Esophageal cancer is a disease with high morbidity and mortality, exploring effective treatment methods is the key to the treatment of this disease. This study aims to compare the clinical efficacy and safety of multi-band mucosectomy (MBM) and endoscopic submucosal dissection (ESD) in the treatment of single early esophageal cancer (EEC) and precancerous lesions, and whether MBM can achieve better clinical effect as an effective treatment method. The clinical data of 70 patients with EEC and precancerous lesions who were treated with MBM and ESD in the Fourth Affiliated Hospital of China Medical University from May 2021 to May 2023 and could be followed up were retrospectively analyzed. They were divided into two groups according to different treatment methods: MBM group (31 cases) and ESD group (39 cases). The general data, perioperative conditions, endoscopic treatment effect and pathological results of the two groups were compared. The duration of endoscopic treatment in MBM group was shorter than that in ESD group [36 (25~39) min vs 46 (41~57) min, p < 0.05], and there was no significant difference in the intraoperative bleeding rate between the two groups (12.90% vs 7.69%, p > 0.05). There was no significant difference in the rate of intraoperative perforation between the two groups (3.23% vs 7.69%, p > 0.05), and the hospitalization time in MBM group was shorter than that in ESD group [5 (4~7) days vs 8 (7~12) days, p < 0.05]. The hospitalization cost was less [2535 (2423~2786) dollars vs 4485 (3858~5794) dollars, p < 0.05]. No postoperative bleeding occurred in both groups. There was no statistically significant difference in postoperative stenosis rate between MBM group and ESD group (3.23% vs 12.82%, p > 0.05), and no statistically significant difference in postoperative local recurrence rate (12.90% vs 5.13%, p > 0.05). There was no significant difference in the rate of additional surgery (9.68% vs 2.56%, p > 0.05). The en bloc resection rate of MBM group was lower than that of ESD group (77.42% vs 97.44%, p < 0.05), but there was no significant difference in the complete resection rate between the two groups (87.10% vs 97.44%, p > 0.05). The postoperative pathological results of MBM group showed 13 cases of low-grade intraepithelial neoplasia (LGIN), 11 cases of high-grade intraepithelial neoplasia (HGIN), and 7 cases of canceration, while the postoperative pathological results of ESD group showed 10 cases of LGIN, 14 cases of HGIN, and 15 cases of canceration, with no statistical significance (p > 0.05). MBM and ESD are effective methods for the treatment of EEC and precancerous lesions. MBM has the advantages of short hospital stay, quick recovery and low cost. However, compared with MBM, ESD can improve the complete resection rate of the lesion, avoid the occurrence of positive incisal margin, and reduce the risk of secondary treatment and additional surgery.