Since 2007, sorafenib is the new standard for the first-line treatment of advanced hepatocellular carcinoma (HCC), with proved effectiveness on survival, but no complete response. We encountered a case of complete and durable response after gemcitabine plus oxaliplatine (GEMOX) in a patient with metastatic HCC. The use of GEMOX was considered because the patient was young, without other liver disease, with bone and hepatic lesions, a rapidly progressive disease, and a poorly differentiated component on histological aspect. After 12 cycles of GEMOX, complete response occurs with disappearance of metastases and normalization of serum level of alpha-fetoprotein. This is the first case report of complete response of HCC to GEMOX. That is why the association of chemotherapy and molecular targeted therapies is a promising direction of research. Our report shows that another important challenge remains in the identification of predictive factors of response to standard chemotherapy or molecular targeted agents.