Background: Previous sorafenib studies in advanced hepatocellular carcinoma (HCC) involved predominantly patients with Child-Pugh A liver cirrhosis, leaving the routine administration of sorafenib to patients with more advanced liver cirrhosis controversial. This study aimed to explore the tolerability and survival benefits in using sorafenib in Child-Pugh B patients. Methods: Advanced HCC patients treated with sorafenib at Queen Mary Hospital, Hong Kong were analyzed retrospectively. Patients were stratified into Child-Pugh A or Child-Pugh B liver cirrhosis. Toxicities were graded according to the NCI CTCAE version 3.0. Results: One hundred and sixty-six advanced HCC patient were included with 106 had underlying Child-Pugh A and 60 Child-Pugh B patients. The age, gender, hepatitis status, disease stages and baseline laboratory parameters between the two groups were similar. The most common treatment related non-haematological grade 3/4 adverse events were hand-foot-syndrome (13.9%), diarrhea (9.7%), rash (7.3%) and malaise (3.6%). Moreover, grade 3/4 neutropenia and thrombocytopenia occurred in 3.0% and 4.9% of the patients in the cohort, respectively. Notably, Child-Pugh A and B patients experienced similar incidence of all these adverse events. Nonetheless, Child-Pugh B patients had higher baseline bilirubin level, and experienced more grade 3 or 4 bilirubinemia during treatment compared with Child-Pugh A patients (33.9% vs. 19.0%, p<0.05). More importantly, Child-Pugh B patients also developed more gastrointestinal bleeding (15% vs. 5.6%, p=0.05) and hepatic encephalopathy (10% vs. 1.9%, p<0.05). Overall, progression free survival was similar among the Child-Pugh A (3.2 months) and B (3.0) patients. However, the overall survival was longer in Child-Pugh A than B patients (6.0 vs 3.9 months, p<0.01). Conclusions: Child-Pugh A and B patients tolerate sorafenib similarly and derive similar survival benefit from the treatment. Nevertheless, Child –Pugh B patients are more susceptible to develop cirrhotic complications during sorafenib treatment, especially hyperbilirubinemia, gastrointestinal bleeding and hepatic encephalopathy.