Objective: To explore the effect of portal vein chemotherapy on liver metastasis after surgical resection of colorectal cancer. Methods: Patients fulfilling the eligibility criteria were assigned to receive either surgery plus 1-week continuous infusion of 5-FU (study group) or surgery alone (observational group). Patients in the study group received portal vein chemotherapy, whereby 5-FU (1000 mg/d) and heparin (5000 IU/d) infusion was initiated from the day of surgery and lasted for 7 consecutive days. Liver metastasis was monitored during five years follow-up postoperatively. Results: Sixty four patients were recruited and assigned to the study group (12 with colon and 20 with rectal cancer) or the control group (10 with colon and 22 with rectal cancer). Liver metastasis rate was 12.5% in study and 25.0% in observational group, the difference being significant (P<0.01). Conclusion: Portal vein chemotherapy could be an effective treatment in preventing liver metastasis after surgical resection of colorectal cancer.