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Objective To compare the clinical efficacy and short-term prognosis of laparoscopic radical resection of right colon cancer guided by superior mesenteric artery and superior mesenteric vein. Methods 80 patients with right colon cancer of cT2-4 and/or N0-2M0 admitted from January 2020 to October 2022 were selected as the research objects, and they were randomly divided into observation group and control group, with 40 patients in each group. The observation group was treated with SMA-oriented laparoscopic radical resection of right colon cancer, while the control group was treated with SMV-oriented laparoscopic radical resection of right colon cancer. The curative effect and prognosis of the two groups were compared. Results There was no significant difference between the two groups in general condition, operation time, gastric tube placement time, recovery time of farting, postoperative fasting time, postoperative drainage time, postoperative nutritional index, total incidence of complications and postoperative hospitalization time(P > 0.05). The lymph nodes in the observation group were significantly more than those in the control group, and the difference was statistically significant(P < 0.05). In the observation group, the lymph nodes in the anterior and left side of superior mesenteric artery were examined (No. D3), and 273 lymph nodes were detected, and Seven patients (17.5%) were diagnosed with D3 metastasis, and 13 lymph nodes were positive (5.2%). Conclusion Laparoscopic radical resection of right colon cancer guided by superior mesenteric artery, without increasing the incidence of complications and high safety, can more thoroughly clean lymph nodes and reduce tumor recurrence, which is expected to significantly improve the prognosis of patients. [ABSTRACT FROM AUTHOR]