diff --git a/akka-remote/src/main/scala/akka/remote/artery/Codecs.scala b/akka-remote/src/main/scala/akka/remote/artery/Codecs.scala
index d3b6d616a29..84a8bf77b3e 100644
--- a/akka-remote/src/main/scala/akka/remote/artery/Codecs.scala
+++ b/akka-remote/src/main/scala/akka/remote/artery/Codecs.scala
@@ -242,7 +242,8 @@ private[remote] object Decoder {
       recipientPath: String,
       inboundEnvelope: InboundEnvelope)
 
-  private object Tick
+  private case object Tick
+  private case object EvictActorRefResolveCache
 
   /** Materialized value of [[Encoder]] which allows safely calling into the operator to interfact with compression tables. */
   private[remote] trait InboundCompressionAccess {
@@ -359,7 +360,8 @@ private[remote] class Decoder(
     inEnvelopePool: ObjectPool[ReusableInboundEnvelope])
     extends GraphStageWithMaterializedValue[FlowShape[EnvelopeBuffer, InboundEnvelope], InboundCompressionAccess] {
 
-  import Decoder.Tick
+  import Decoder.{ EvictActorRefResolveCache, Tick }
+
   val in: Inlet[EnvelopeBuffer] = Inlet("Artery.Decoder.in")
   val out: Outlet[InboundEnvelope] = Outlet("Artery.Decoder.out")
   val shape: FlowShape[EnvelopeBuffer, InboundEnvelope] = FlowShape(in, out)
@@ -395,6 +397,9 @@ private[remote] class Decoder(
         val tickDelay = 1.seconds
         scheduleWithFixedDelay(Tick, tickDelay, tickDelay)
 
+        val evictDelay = 60.seconds // FIXME config
+        scheduleWithFixedDelay(EvictActorRefResolveCache, evictDelay, evictDelay)
+
         if (settings.Advanced.Compression.ActorRefs.Enabled) {
           val d = settings.Advanced.Compression.ActorRefs.AdvertisementInterval
           scheduleWithFixedDelay(AdvertiseActorRefsCompressionTable, d, d)
@@ -584,6 +589,9 @@ private[remote] class Decoder(
             tickMessageCount = messageCount
             tickTimestamp = now
 
+          case EvictActorRefResolveCache =>
+            actorRefResolver.clearRemovedAssociations()
+
           case AdvertiseActorRefsCompressionTable =>
             compressions
               .runNextActorRefAdvertisement() // TODO: optimise these operations, otherwise they stall the hotpath
diff --git a/akka-remote/src/main/scala/akka/remote/artery/LruBoundedCache.scala b/akka-remote/src/main/scala/akka/remote/artery/LruBoundedCache.scala
index 59e8d4832e2..8a7f205d5ac 100644
--- a/akka-remote/src/main/scala/akka/remote/artery/LruBoundedCache.scala
+++ b/akka-remote/src/main/scala/akka/remote/artery/LruBoundedCache.scala
@@ -59,6 +59,9 @@ private[akka] abstract class LruBoundedCache[K: ClassTag, V <: AnyRef: ClassTag]
     find(position = h & Mask, probeDistance = 0)
   }
 
+  final def valuesIterator(): Iterator[V] =
+    values.iterator.filterNot(_ eq null)
+
   final def stats: CacheStatistics = {
     var i = 0
     var sum = 0
diff --git a/akka-remote/src/main/scala/akka/remote/serialization/ActorRefResolveCache.scala b/akka-remote/src/main/scala/akka/remote/serialization/ActorRefResolveCache.scala
index 410938bb9d3..47df0a7adb3 100644
--- a/akka-remote/src/main/scala/akka/remote/serialization/ActorRefResolveCache.scala
+++ b/akka-remote/src/main/scala/akka/remote/serialization/ActorRefResolveCache.scala
@@ -4,6 +4,8 @@
 
 package akka.remote.serialization
 
+import scala.concurrent.duration.Deadline
+import scala.concurrent.duration.FiniteDuration
 import scala.reflect.ClassTag
 
 import akka.actor.ActorRef
@@ -35,12 +37,20 @@ private[akka] object ActorRefResolveThreadLocalCache
 
   override def createExtension(system: ExtendedActorSystem): ActorRefResolveThreadLocalCache =
     new ActorRefResolveThreadLocalCache(system)
+
+  private final case class ActorRefResolveCacheHolder(cache: ActorRefResolveCache, evictDeadine: Deadline)
 }
 
 /**
  * INTERNAL API
  */
 private[akka] class ActorRefResolveThreadLocalCache(val system: ExtendedActorSystem) extends Extension {
+  import ActorRefResolveThreadLocalCache.ActorRefResolveCacheHolder
+
+  val evictInterval: FiniteDuration = {
+    import scala.concurrent.duration._
+    60.seconds // FIXME config
+  }
 
   private val provider = system.provider match {
     case r: RemoteActorRefProvider => r
@@ -50,12 +60,21 @@ private[akka] class ActorRefResolveThreadLocalCache(val system: ExtendedActorSys
         s"not with ${system.provider.getClass}")
   }
 
-  private val current = new ThreadLocal[ActorRefResolveCache] {
-    override def initialValue: ActorRefResolveCache = new ActorRefResolveCache(provider)
+  private val current = new ThreadLocal[ActorRefResolveCacheHolder] {
+    override def initialValue: ActorRefResolveCacheHolder = {
+      ActorRefResolveCacheHolder(new ActorRefResolveCache(provider), Deadline.now + evictInterval)
+    }
   }
 
-  def threadLocalCache(@unused provider: RemoteActorRefProvider): ActorRefResolveCache =
-    current.get
+  def threadLocalCache(@unused provider: RemoteActorRefProvider): ActorRefResolveCache = {
+    val holder = current.get
+    val cache = holder.cache
+    if (holder.evictDeadine.isOverdue()) {
+      cache.clearRemovedAssociations()
+      current.set(ActorRefResolveCacheHolder(cache, Deadline.now + evictInterval))
+    }
+    cache
+  }
 
 }
 
@@ -91,6 +110,19 @@ private[akka] abstract class AbstractActorRefResolveCache[R <: ActorRef: ClassTa
     ref
   }
 
+  /**
+   * Invalidate cachedAssociation in all RemoteActorRef entries where the `Association` is removed.
+   */
+  def clearRemovedAssociations(): Unit = {
+    valuesIterator().foreach {
+      case r: RemoteActorRef =>
+        val cachedAssociation = r.cachedAssociation
+        if (cachedAssociation != null && cachedAssociation.isRemovedAfterQuarantined())
+          r.cachedAssociation = null
+      case _ =>
+    }
+  }
+
   override protected def compute(k: String): R
 
   override protected def hash(k: String): Int = Unsafe.fastHash(k)