Objective To compare the application effects of high-frequency electric knife, CO2 laser and surgical resection of fine suture in patients with pigmented nevus of the skin. Methods A total of 360 patients with pigmented nevus of the skin admitted to the Department of Dermatology, Xunyang People's Hospital from July 2019 to July 2022 were selected as the research objects. According to different treatment methods, they were divided into group A (n =113), group B (n =120) and group C (n =127). Group A received high-frequency electric knife treatment, group B received CO2 laser treatment, and group C received surgical resection of fine suture treatment. The clinical efficacy and adverse reactions of the three groups were compared. Results The total effective rate of treatment in group C was 97.64%, which was higher than 82.30% in group A and 85.83% in group B, the difference was statistically significant (P <0.05). The incidence of adverse reactions in group C was 1.57%, which was lower than 12.39% in group A and 10.00 % in group B, the difference was statistically significant (P <0.05). Conclusion High-frequency electric knife, CO2 laser and surgical resection of fine suture are effective in the treatment of pigmented nevus of the skin, but compared with highfrequency electric knife and CO2 laser, surgical resection of fine suture is more effective and safe, and can be used as the first choice for clinical treatment of skin pigmented nevus.