Background : Thalidomide has been reported to have antitumor activity for treating metastatic hepatocellular carcinoma (HCC). We evaluated the safety and efficacy of using thalidomide for treating selected patients with unresectable or metastatic HCC, and their disease was refractory to systemic chemotherapy. Methods : Eight patients with measurable and metastatic HCC that had progressed with prior systemic chemotherapy and who desired further active therapy were enrolled in this study. Thalidomide was given orally at bedtime and it was started at 200 mg/day with no further dose escalation. The response was measured at 2-month intervals. Results : The median age was 44 years (range: 34-52 years) and all the patients had received doxorubicin-based systemic chemotherapy prior to their enrollment. Each patient received thalidomide for a median of 152 days (range: 5-422 days). One partial response was observed (12.5%, 95% CI; 0-42%) along with 4 cases of stable diseases. The most commonly encountered toxicity was somnolence; grade 3 somnolence was noted for one patient, which led to treatment discontinuation. Skin rash was observed in one responding patient. Conclusions : The results indicate that thalidomide may feasibly offer disease stabilization to metastatic HCC patients. Further dose escalation of thalidomide, or its combination with other chemotherapeutic agents, may be of interest and this should be investigated for treating patients with metastatic HCC.