diff --git a/sql/core/src/main/scala/org/apache/spark/sql/execution/columnar/InMemoryTableScanExec.scala b/sql/core/src/main/scala/org/apache/spark/sql/execution/columnar/InMemoryTableScanExec.scala
index c7ddec55682e..72cf998427bf 100644
--- a/sql/core/src/main/scala/org/apache/spark/sql/execution/columnar/InMemoryTableScanExec.scala
+++ b/sql/core/src/main/scala/org/apache/spark/sql/execution/columnar/InMemoryTableScanExec.scala
@@ -102,6 +102,7 @@ case class InMemoryTableScanExec(
     case IsNull(a: Attribute) => statsFor(a).nullCount > 0
     case IsNotNull(a: Attribute) => statsFor(a).count - statsFor(a).nullCount > 0
 
+    case In(_: AttributeReference, list: Seq[Expression]) if list.isEmpty => Literal.FalseLiteral
     case In(a: AttributeReference, list: Seq[Expression]) if list.forall(_.isInstanceOf[Literal]) =>
       list.map(l => statsFor(a).lowerBound <= l.asInstanceOf[Literal] &&
         l.asInstanceOf[Literal] <= statsFor(a).upperBound).reduce(_ || _)
diff --git a/sql/core/src/test/scala/org/apache/spark/sql/execution/columnar/InMemoryColumnarQuerySuite.scala b/sql/core/src/test/scala/org/apache/spark/sql/execution/columnar/InMemoryColumnarQuerySuite.scala
index 8d411eb191cd..75d17bc79477 100644
--- a/sql/core/src/test/scala/org/apache/spark/sql/execution/columnar/InMemoryColumnarQuerySuite.scala
+++ b/sql/core/src/test/scala/org/apache/spark/sql/execution/columnar/InMemoryColumnarQuerySuite.scala
@@ -429,4 +429,19 @@ class InMemoryColumnarQuerySuite extends QueryTest with SharedSQLContext {
       checkAnswer(agg_without_cache, agg_with_cache)
     }
   }
+
+  test("SPARK-22249: IN should work also with cached DataFrame") {
+    val df = spark.range(10).cache()
+    // with an empty list
+    assert(df.filter($"id".isin()).count() == 0)
+    // with a non-empty list
+    assert(df.filter($"id".isin(2)).count() == 1)
+    assert(df.filter($"id".isin(2, 3)).count() == 2)
+    df.unpersist()
+    val dfNulls = spark.range(10).selectExpr("null as id").cache()
+    // with null as value for the attribute
+    assert(dfNulls.filter($"id".isin()).count() == 0)
+    assert(dfNulls.filter($"id".isin(2, 3)).count() == 0)
+    dfNulls.unpersist()
+  }
 }