This case report describes Crohn's disease complicated by squamous cell carcinoma in an enterocutaneous fistula. A 48-year-old male patient was diagnosed with Crohn's disease 24 years ago and has undergone five surgical operations. An enterocutaneous fistula originated from the midline abdominal wound 11 years after the onset. Azathioprine was initiated instead of surgery due to frequent recurrence of the fistula and his short residual small intestine (approximately 170cm). We followed him every 3 months and continued prescribing azathioprine as his fistula secretions decreased and became manageable. He noticed a mass at the same site 13 years after the appearance of the enterocutaneous fistula which was diagnosed as squamous cell carcinoma through biopsy. The tumor was markedly reduced after preoperative chemoradiotherapy. We resected the affected intestinal tract and abdominal wall associated with the enterocutaneous fistula, and he acheived a pathological complete response. Squamous cell carcinoma originating from an enterocutaneous fistula in Crohn's disease is rare;however, long-standing inflammatory lesions should be carefully monitored for carcinogenesis.