OBJECTIVE To investigate the effect of omega-3 polyunsaturated fatty acids (PUFA) on postoperative inflammatory response and clinical efficacy in gastric cancer patients with nutritional risk. METHODS All patients with gastric cancer in our department from June 2013 to January 2014 undergoing radical gastrectomy were prospectively enrolled in the study. Patients who matched the selection criteria were randomly divided into two groups: trial group (with omega-3 PUFA in parenteral nutrition) and control group (without omega-3 PUFA in parenteral nutrition). Levels of inflammatory factors (serum CRP, TNF-α, IL-1, IL-6, IL-10) and nutrition-related proteins (prealbumin, retinol conjugated protein and transferrin) were compared between the two groups before operation and 2, 4 and 6 days after operation. Incidence of postoperative systemic inflammatory response syndrome (SIRS) and other indicators associated with efficacy were compared between the two groups as well. RESULTS Forty-seven patients were finally included in this study with 21 patients in the trial group and other 26 in the control group. There were no significant differences of inflammatory factors and nutrition-related proteins between the two groups before operation (all P>0.05). In the 6th days after operation, the levels of proinflammatory cytokines, including CRP, IL-1 and IL-6 were significantly lower in the trial group as compared to the control group, while the level of IL-10 (inhibiting inflammatory cytokine) was higher in the trial group, as well as levels of nutrition proteins(all P<0.05). The trial group had significantly lower rate of SIRS than the control group [57.1%(12/21) vs. 84.6% (22/26), P=0.036]. Compared with the control group, patients in the trial group had shorter bowel sound recovery time [(12.3±1.1) d vs. (3.1±1.3) d, P=0.025], earlier passage of flatus [(3.1±1.0) d vs. (3.9±1.2) d, P=0.025] and shorter hospital stay [(9.4±2.1) d vs. (10.9±2.5) d, P=0.038], but there was no difference in postoperative complication rate between the two groups (P=0.678). CONCLUSIONS Omega-3 PUFA can reduce the release of inflammatory promoters, promote the release of inhibiting inflammatory cytokine IL-10, decrease the incidence of SIRS, improve patients' nutritional state, expedite the recovery of gastrointestinal function and shorten patients' recovery time.