Abstract: Objective To explore the effect of laparoscopic total mesocolic resection (TME) on microRNA-101, T cell subsets and local recurrence rate in patients with right colon cancer after operation. Methods From March 2015 to April 2017, 86 patients with right colon cancer were randomly divided into control group (n = 43) and research group (n = 43). The control group was treated with traditional laparotomy, while the study group was treated with 3D laparoscopic total mesocolon resection. The perioperative conditions, serum T cell subsets (CD3+, CD4+, CD8+, CD4+/CD8+) levels, microRNA-101 water and the incidence of complications before and after operation were analyzed. The local recurrence rates of the two groups were followed up for 6 to 12 months. Results Perioperative condition: There was no significant difference in the number of lymph node dissection between the study group and the control group (P > 0.05). The blood loss in the study group was less than that in the control group. The operation time, anal exhaust time, hospitalization time and starting eating time in the study group were shorter than that in the control group (P < 0.05). T cell subsets: On the first day after operation, the levels of CD3+, CD4+, CD4+/CD8+ in the two groups were lower than that before operation, and the serum levels of CD3+, CD4+, CD4+/CD8+ increased on the 3rd day after operation, and CD8+ decreased on the 1st day after operation (P < 0.05). The serum levels of CD3+, CD4+, CD8+ and CD4+/CD8+ in the study group were higher than that in the control group (P < 0.05). MicroRNA-101: There was no significant difference in microRNA-101 level between the two groups before operation (P > 0.05). There was no significant difference in microRNA-101 levels between the two groups after operation (P > 0.05). The level of microRNA-101 was higher than that of the control group (P < 0.05). The local recurrence rate: the local recurrence rate of the study group at 6 and 9 months after operation (0.00% and 4.65%) was not significantly different from that of the control group (6.98% and 13.95%) (P > 0.05). The local recurrence rate of the study group at 12 months after operation (4.65%) was lower than that of the control group (P < 0.05). Complications: The incidence of complications in the study group (6.98%) was lower than that in the control group (23.26%) with statistical significance (P < 0.05). Conclusion 3D laparoscopic total mesocolic resection for right colon cancer is effective in lymph node dissection. It can reduce surgical trauma and the injury of immune function caused by surgery, improve the level of microRNA-101, and decrease the risk of local recurrence and the incidence of complications. It is safe and conducive to improving the prognosis.