Objective To investigate the effect of different administration time of flurbiprofen axetil (FA) on postoperative immune function of patients undergoing radical resection of colon cancer. Methods A total of 124 patients who were scheduled for laparoscopic resection of colon cancer under general anesthesia were selected. According to the random number table method, they were divided into four groups (n=31): a preoperative administration group (group Pre), an intraoperative administration group (group Intra), a postoperative administration group (group Post) and a control group (group Control). On the basis of the same other anesthetics in the 4 groups, group Pre was slowly intravenously injected with FA 100 mg 10 min before induction of anaesthesia, group Intra was slowly intravenously injected with FA 100 mg 1 h after the establishment of the pneumoperitoneum, group Post was slowly intravenously injected with FA 100 mg at the end of suturing, and group Control did not administered with FA. Collect patient demographic characteristics, surgery‑related information, and intraoperative conditions. The levels of CD4+, CD4+/CD8+, tumor necrosis factor‑α (TNF⁃α) and interleukin‑6 (IL⁃6) in peripheral blood were recorded 15 min before induction of anesthesia (T0), 24 h after surgery (T2), 48 h after surgery (T3) and 72 h after surgery (T4). Their Visual Analogue Scale (VAS) scores at the end of surgery (T1), T2, T3 and T4 were recorded. The postoperative complications, tumor recurrence‑free and overall survival rate 1 year after surgery were also recorded. Results The amounts of remifentanil used in groups Pre and Intra were less than those in groups Post and Control (P<0.05). There was no statistical difference in the levels of CD4+, CD4+/CD8+, TNF⁃α and IL⁃6 at T0 in the four groups (P>0.05). Compared with those at T0: the four groups presented decreases in the levels of CD4+ and CD4+/CD8+ at T2 (P<0.05), increases in TNF‑α and IL‑6 at T2 to T4 (P<0.05). Compared with those in group Control: the levels of CD4+ increased at T2 in group Pre, Intra and Post, increased at T3 in group Pre and Intra, increased at T4 in group Pre (P<0.05); the ratio of CD4+/CD8+ increased at T2 and T3 in group Pre and Intra, increased at T4 in group Pre (P<0.05); the levels of TNF‑α decreased at T2 and T3 in group Pre, Intra and Post, decreased at T4 in group Pre and Intra (P<0.05); the levels of IL‑6 decreased at T2 and T4 in group Pre, Intra and Post, decreased at T3 in group Pre and Intra (P<0.05). Compared with group Post: the levels of CD4+ increased at T3 and T4 in group Pre, the levels of IL‑6 decreased at T4 in group Pre (P<0.05). Compared with group Intra: the levels of CD4+ and CD4+/CD8+ increased at T4 in group Pre (P<0.05). The rest and coughing VAS scores in group Pre, Intra and Post were lower than group Control at T1 (P<0.05). There was no significant difference in postoperative complications between the four groups (P>0.05). There was one case of tumor recurrence in each of group Pre and group Control, and there was no death in each group within one year, there was no significant difference between the two groups (P>0.05). Conclusion Preoperative intravenous FA has a protective effect on the immune function of patients undergoing radical resection of colon cancer, which is better than intraoperative and postoperative administration.