Abstract: OBJECTIVE To observe the clinical effect of mosapride combined with fluoxetine on postoperative gastrointestinal dysfunction (PGD) of colorectal cancer patients. METHODS Collected 58 PGD patients who were received radical operation for colorectal cancer from December 2015 to December 2016 and randomly divided into three groups:routine group(20 cases) treated with basic nurse, separate group(19 cases) treated with mosapride and basic nurse, combined group(19 cases) treated with fluoxetine on the basis of separate group's treatment. To observe and compare the recovery of gastrointestinal function (bowl sounds scores, first exhaust defecation time and length of stay), the level of gut hormone in peripheral bloodmotilin (MTL) and somatostatin(SS) and the change of self-rating depression score as well as the total efficacy of 3 groups. RESULTS On the 3rd and 5th day after operation, compared with the routine group, there were significantly increase of bowl sounds scores in the combined group(P<0.05, P<0.01); the first exhaust defecation time and length of stay distinctly shorter in combined group(P<0.05). The level of MTL significantly increased and SS decreased in combined group (P<0.05) after treated. The result of self-rating depression scale showed that the score of combined group were higher than the other two groups(P<0.05). There were statistical significance in total efficacy of the 3 groups, the total efficacy of combined group were better than the other two groups(P<0.05). CONCLUSION Mosapride combined with fluoxetine can improve the curative effect of postoperative gastrointestinal dysfunction in patients with colorectal cancer and can shorten the treatment period as well as promote the recovery of gastrointestinal function.