Objective To explore the effectiveness of folded transverse superficial epigastric artery perforator flap in repairing the large penetrating defect after buccal carcinoma resection. Methods Between January 2019 and June 2021, 12 patients with buccal squamous cell carcinoma were treated. There were 6 males and 6 females with an average of 66.9 years (range, 53-79 years). The pathological stage was T3a-T4b, and the preoperative mouth opening was (3.08±0.46) cm. The disease duration ranged from 6 to 24 months, with an average of 15 months. After buccal carcinoma radical resection and neck lymph node dissection, the penetrating defects in size of 8 cm×6 cm to 16 cm×8 cm and in depth of 0.5-1.5 cm were remained. The transverse superficial epigastric artery perforator flap in size of 8 cm×6 cm to 14 cm×8 cm were harvested and folded to repair the penetrating defects. The donor site was sutured directly. Results All 12 skin flaps survived after operation, and the wounds healed by first intention. No internal or external fistula complications occurred. All incisions at the recipient site healed by first intention. All patients were followed up 12-18 months (mean, 14 months). There was no obvious abnormality in the color and texture of the flap, the oral and facial appearances were symmetrical, and there was no obvious swelling in the cheek. At last follow-up, the patient’s mouth opening was (2.89±0.33) cm, which was not significantly different from that before operation (t=1.879, P=0.087). The subjective satisfaction scores of 12 patients were 6-8 points, with an average of 7.3 points. Significant scars remained at the donor site but concealed in location. Conclusion The folded transverse superficial epigastric artery perforator flap can be used as a surgical method for repairing large penetrating defects after the buccal carcinoma resection, with a good recovery of facial appearance and oral function.