[Abstract] Objective To observe the efficacy and safety of endoscopic submucosal dissection (ESD) in the treatment of rectal/anal lesions involving the dentate line. Methods A retrospective analysis was conducted on the case data of 13 patients with rectal/anal lesions involving the dentate line who underwent ESD in the Department of Digestive Endoscopy at Jiangsu Provincial Hospital from January 2022 to July 2023. The efficacy and safety of ESD treatment were evaluated. Results ESD was performed on a total of 14 lesions involving the anal canal in 13 patients. The lesions had a length of 1.4 to 12.5 cm, with an average of (5.4±3.8) cm. All lesions were resected entirely in a single session, with an R0 resection rate of 92.31%. The ESD procedure duration ranged from 35 to 225 minutes, with an average of (88.3±53.76) minutes. Postoperatively, one patient developed anal stenosis, which improved after treatment with anal dilatation; no delayed bleeding, perforation, or other complications occurred. Pathological examination after ESD revealed 6 instances of tubulovillous adenoma, 2 instances of tubular adenoma, 3 instances of tubular adenocarcinoma, and 2 instances of squamous epithelial intraepithelial neoplasia (all associated with HPV infection). In one case of tubular adenocarcinoma, the local resection margin showed focal tubulovillous adenoma, while the margins around and at the base of the lesion were negative. The median follow-up time was 7.0 months (range: 2–13 months), with no local residue or recurrence/metastasis observed. Conclusion ESD is a safe and effective treatment for early cancer or precancerous lesions involving the early anal canal and is worthy of clinical promotion and application.