Background: In patients with advanced hepatocellular carcinoma (HCC), inferior vena cava/intra-right atrial (IVC/RA) tumor thrombi are not uncommon findings and are usually associated with extremely poor outcome. Surgical interventions as well as nonsurgical approaches, such as transcatheter arterial chemoembolization and radiotherapy, have been used in the treatment of patients with symptomatic IVC/RA tumor thrombi. However, such therapeutic modalities are usually not feasible when a patient shows poor general performance, the presence of metastatic disease, and underlying hepatic dysfunction. Such patients show limited survival. Material and Methods: Herein we describe 3 patients with advanced-stage HCC whose IVC/RA tumor thrombi and primary tumors regressed remarkably after low-dose thalidomide (200-400 mg/day) therapy. An Entrez PUBMED search of English Literature articles was performed to identify other cases of RA tumor thrombi in HCC who had received various treatments. Results: Two of our patients survived for more than 15 months after the diagnosis of IVC/RA tumor thrombi, while the other had effective symptomatic palliation associated with a drastic fall of AFP serum levels and significant tumor regression within 4 weeks of thalidomide therapy. A literature review suggested that the survival of our patients is comparable with that of occasional patients who had received aggressive surgical intervention. Conclusions: Our results suggest that, despite the low tumor response rate in earlier studies, thalidomide therapy may sometimes provide effective palliation for patients with far advanced HCC with symptomatic IVC/RA tumor thrombi and who are not candidates for alternative treatment options.