Cell-cell fusion is widely observed during development and disease conditions, including fertilization, myogenesis, and trophoblast formation. Cell fusion brings a dramatic change to participating cells so it should be tightly controlled, but the underlying mechanism is poorly understood. We found that the JAK/STAT pathway suppressed cell fusion during wound healing and delimited the event to the vicinity of the wound in the Drosophila larval epidermis. In the absence of JAK/STAT signaling, a large syncytium containing 3-fold the number of nuclei observed in wild-type tissue formed in wounded epidermis. JNK was activated in the wound vicinity and activity peaked at approximately 8 h after injury, whereas JAK/STAT signaling was activated in an adjoining concentric ring and activity peaked at a later stage. Cell fusion occurred primarily in the wound vicinity, where JAK/STAT activation was suppressed by fusion-inducing JNK signaling. We found that the balance of JAK/STAT and JNK signaling determined whether cell fusion was executed or not. JAK/STAT signaling was both necessary and sufficient for the induction of βPS integrin expression, suggesting that the suppression of cell fusion was mediated by integrin protein.