To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for the treatment of symptomatic giant colonic lipomas (≥5 cm). Eight patients with giant colonic lipomas were treated with ESD at the Department of Digestive Endoscopy, Shanghai East Hospital from December 2018 to December 2021. The complete resection rate was 100% with the mean size of the resected lesion of 6.0 cm (ranging from 5.5 cm to 9.0 cm). The mean operation time of ESD was 41 minutes (ranging from 25 minutes to 80 minutes). Minimal bleeding were all successfully stopped with electrocoagulation and 2 small perforations were successfully sutured during the procedures. No abdominal pain, fever, delayed bleeding or perforation occurred after ESD. The mean hospital stay was 3 days (ranging from 3 days to 5 days). No residual or recurrence was found during the follow-up of 8-36 months. Thus, ESD is safe and effective for the treatment of giant colonic lipomas which can avoid surgical resection.