Objective To explore the effects of dexmedetomidine combined with sufentanil on the analgesic effect, immune function and stress response of patients after radical resection of colon cancer.Methods A total of 96 patients who underwent radical resection of colon cancer in our hospital between July 2016 and July 2018 were randomly divided into observation group (n=48) and control group (n=48). Patients in the two groups were given the same operating anesthesia, and all had self-controlled analgesia. The patients in control group were given 1.0 μg?kg^-1?d^-1 sufentanil + 8.0 mg tropisetron, and those in observation group were given 1.5 μg?kg^-1?d^-1 dexmedetomidine + 1.0 μg?kg^-1?d^-1 sufentanil + 8.0 mg tropisetron. The changes of analgesic effect (VAS and Ramsay scores), immune function (levels of IgG, IgA, IgM, CD4⁺ and CD8⁺), stress level [adrenocorticotropic hormone (ACTH), hydrocortisone (Cor) and aldosterone (ALD)], serum levels of S-100β and neuron-specific enolase (NSE), and adverse reactions of the two groups were evaluated at 0 h (T1), 4 h (T2), 8 h (T3), 24 h (T4) after operation.Results There were significant differences in analgesic effect between the two groups. The VAS scores of the observation group at T2, T3 and T4 were respectively lower than those of the control group (P<0.05). The Ramsay scores of the observation group at T2, T3 and T4 were respectively higher than those of the control group (P<0.05). At T4 time point, the levels of IgG, IgA, IgM, CD4⁺ T cells of the observation group were significantly higher than those of the control group (P<0.05), while the CD8⁺ level of the observation group were significantly lower than that of the control group (P<0.05). The levels of ACTH, Cor and ALD were significantly lower in the observation group than in the control group (P<0.05). There were no significant differences in the serum levels of S-100β and NSE at T1 between the two groups (P>0.05). At T4, the serum levels of S-100β and NSE were significantly lower in the observation group than in the control group (P<0.05). As for drug safety, the incidence of nausea and vomiting in the observation group was significantly lower than that in the control group (6.25% vs. 20.83%, P<0.05), and the incidence of bradycardia in the observation group was significantly higher than that in the control group (20.83% vs. 6.25%, P<0.05).Conclusion Dexmedetomidine combined with sufentanil has better analgesic effect on patients with radical resection of colon cancer. It can enhance the immune function, alleviate stress response and reduce serum S-100β and NSE levels of patients after colon cancer operation.