Objective To investigate effects of fast track surgery (FTS) combined with laparoscopy on perioperative inflammatory mediators, immune indices, and clinical short-term recovery effect in patient with colorectal cancer. Methods A prospective randomized controlled trial was conducted. The patients underwent laparoscopic colorectal cancer surgery at the Department of Gastrointestinal Surgery, The Third People’s Hospital of Chengdu from July 2014 to March 2017 were included in this study. The patients were randomly divided into FTS group and traditional group by the random digital table. The FTS mode and the traditional method were adopted during the perioperative period in the FTS group and the traditional group respectively. The inflammatory mediators such asC reactive protein (CRP) and interleukin 6 (IL-6) and cellular immune indexes such as CD4, CD8 and CD4/CD8 on the preoperative 1 d, postoperative 1 d, 3 d and 7 d, as well as the index of clinical short-term rehabilitation were compared between these 2 groups. Results ① Eighty-four patients were included in this study, there were 43 patients in the FTS group and 41 patients in the traditional group. There were no significant differences in the baseline characteristics and the surgical-related indicators between the two groups (P>0.050). ② There were no significant difference in the levels of CRP and IL-6 between the two groups at different time points (P>0.050). The change trend of CRP and IL-6 levels in FTS group and traditional group before and after operation were the same, the CRP and IL-6 levels at the first day after operation were significantly higher than those on 1 d before operation (P<0.001), but on the 7th day after operation decreased significantly. ③ There were no significant difference of CD4, CD 8 and CD4/CD8 levels between the two groups at different time points (P>0.050). The CD4 decreased significantly in 2 groups at the first day after operation (P<0.050), it began to rise on the 3rd day after operation and was close to the preoperative level on the 7th day after operation, but the increase in the traditional group was smaller. The changes of CD8 level at different time points before and after operation were not significant in two groups (P>0.050). The changes of CD4/CD8 ratio at different time points before and after operation were not significant in two groups (P>0.050), only the first day after operation of FTS group was significantly lower than that in preoperative 1 d (P<0.001), and on the third day after operation, it increased significantly and was close to the level of 1 day before operation. ④ The time of the first postoperative anal exhaustion or defecation in the FTS group was significantly shorter than that in the traditional group (P<0.001). The overall incidence of postoperative complications and the incidence of hypoproteinemia in the FTS group were significantly lower than those in the traditional group (P<0.050). Conclusion Compared with traditional perioperative management in combination with laparoscopic surgery, FTS combined with laparoscopic surgery has no effects on postoperative inflammatory mediators and immune parameters in patient with colorectal cancer, and it could reduce complications, reduce traumatic stress, and accelerate postoperative recovery for patient with colorectal cancer.