We report here the efficacy of radioembolization followed by sorafenib in unresectable HCC in the Phase II study. This study represents the first prospective Phase II evaluation of sequential radioembolization-sorafenib therapy in patients from Asia-Pacific region. The majority of patients included in this trial had advanced HCC and a high tumor burden in the liver, and were not ideal candidates for TACE. The combination of radioembolization-sorafenib appears to be manageable and consistent with previously published experience with each treatment. Excluding hand-foot syndrome, 23% of events were grade 3 or above. Most events were transient and managed with sorafenib dose adjustments or WZ8040 discontinuation. By comparison, treatment-emergent adverse events were reported in 98% of patients in the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol study. The evaluation of the combination of doxorubicin-eluting beads with sorafenib found that most patients experienced at least one grade 3 to 4 toxicity, the most common being grade 3–4 fatigue in 36% of patients, and required dose reductions in 73% of patients. By comparison, the most commonly reported adverse event with radioembolization was fatigue occurring in 54% of patients, including 2% with grade 3 events, with an increase in total bilirubin reported as the most commonly reported grade 3+ event in 6% of patients at 3 months post-treatment. The incentive for therapeutic intervention to palliate symptoms or extend survival of HCC must be balanced against the degree of hepatic functional reserve and the ability of the patient to tolerate the procedure. Compromised hepatic function as manifested by thrombocytopenia, excessive elevations in transaminases and bilirubin, jaundice and ascites were reported in 14% of patients following radioembolization-sorafenib in this study. These cases resolved upon withdrawal of sorafenib and the administration of steroid therapy. Liver dysfunction with sorafenib is a rare event. The risk of radioembolization-induced liver disease reported by Sangro et al 2008 increased significantly with high total bilirubin, jaundice and ascites in the absence of overt tumor progression and/or bile duct dilatation. As advised by Lau et al 2012, the dose for uninvolved, normal parenchyma should never be.70 Gy and should preferably remain,50 Gy with some institutions, especially in Asia, having set even lower thresholds of 40–43 Gy. Further study by Sangro et al 2013 has shown that the frequency and severity of this complication can be significantly reduced through modifications to the activity calculations, combined with lowering the threshold for radioembolization from a total bilirubin of 3 to 2 mg/dL and the routine use of ursodeoxycholic acid and low-dose steroid over the two months post-radioembolization. There was one case of thrombocytopenia which was a modest event at 3.5 months post-treatment followed by patient death due to progressive disease 2 months later. Thrombocytopenia has been commonly observed in HCC patients following sorafenib administration and has been rarely reported following radioembolization.