To investigate the effect of omega-3 polyunsaturated fatty acids (PUFA) on postoperative inflammatory response and clinical efficacy in colorectal cancer patients with laparoscopic surgery. Methods All the patients with colorectal cancer undergoing laparoscopic surgery in our department from February 2014 to May 2015 were prospectively enrolled in the study. The patients who matched the selection criteria were randomly divided into two groups: trial group (with omega-3 PUFA in parenteral nutrition preparations) and control group (without omega-3 PUFA in parenteral nutrition preparations). Levels of inflammatory factors (serum CRP, procalcitonin and IL-6) and nutrition-related proteins (albumin, prealbumin, retinol conjugated protein and transferrin) were compared between the two groups before operation and on the 1st and 6th day after operation. Other clinically relevant indicators were compared between the two groups as well. Results There were no significant differences in inflammatory factors or nutrition related proteins between the two groups before operation ( p> 0.05). The levels of C reactive protein, procalcitonin and IL-6 were significantly different at different time points ( p<0.05). There were significant differences in the levels of C reactive protein, procalcitonin and IL-6 between the two groups (p <0.05). On the 6th day after operation, the levels of inflammatory cytokines, including CRP, procalcitonin and IL-6 in the trial group were significantly lower than those of the controlgroup (p < 0.05). The variation trends of inflammatory factors were significantly different between the two groups( p< 0.05). Conclusions Omega-3 PUFA can reduce the release of inflammatory factors, lower the incidences of postoperative complications, and expedite postoperative recovery.