Omega-3 fatty acid supplemented total parenteral nutrition improves the clinical outcome of patients undergoing certain operations; however, its benefits for patients with hepatitis type B virus (HBV)-associated hepatocellular carcinoma (HCC) who have undergone hepatectomy are still not clear. The aim of this study was to evaluate the effect of omega-3 fatty acid supplemented total parenteral nutrition on the clinical outcome of patients with HBV-associated HCC who underwent hepatectomy at our institution. A total of 63 patients with HBV-associated HCC who underwent hepatectomy were included in this study. These patients were randomly assigned to receive standard total parenteral nutrition (the control group, n = 31) or omega-3 fatty acid supplemented total parenteral nutrition (the omega-3 fatty acid group, n = 32) for at least 5 d. The study endpoints were the occurrence of infection-related complications, recovery of liver function and length of hospital stay. The results showed that the omega-3 fatty acid group had a lower infection rate (omega-3 fatty acid, 19.4% vs control, 43.8%, P < 0.05), a better liver function after hepatectomy: alanine transaminase (omega-3 fatty acid, 48.23±18.48 U/L vs control, 73.34±40.60 U/L, P < 0.01), aspartate transaminase (omega-3 fatty acid, 35.77±14.56 U/L vs control, 50.53±24.62 U/L, P < 0.01), total bilirubin (omega-3 fatty acid, 24.29±7.40 mmol/L vs control, 28. 37±8.06 mmol/L, P < 0.05) and a shorter length of hospital stay (omega-3 fatty acid, 12.71±2.58 d vs control, 15.91±3.23 d, P < 0.01). The serum contents of IL-6 (omega-3 fatty acid, 23.98±5.63 pg/mL vs control, 35.55±7.5 pg/mL, P < 0.01) and TNF-α (omega-3 fatty acid, 4.43±1.22 pg/mL vs control, 5.96±1.58 pg/mL, P < 0.01) after hepatectomy were significantly lower in the omega-3 fatty acid group than those of the control group. In conclusion, administration of omega-3 fatty acid may reduce infection rate and improve liver function recovery in HBV-associated HCC patients after hepatectomy. This improvement is associated with suppressed production of proinflammatory cytokines in these patients.