 The primary objective of this phase I dose escalation study is to determine the maximum tolerated dose of TH-302 when administered with doxorubicin via trans-arterial chemo-embolization TACE in patients with hepatocellular carcinoma HCC who are not transplant candidates and have unresectable disease. HCC is the second leading cause of worldwide cancer death and is generally incurable without liver transplant. TACE can convert about 40 of these patients to transplant candidates. Additionally, in non-transplant HCC patients, TACE confers statistical improvements in overall survival. Selective HCC arterial catheterization during TACE allows for the delivery of concentrated drugs to the liver tumor but the optimal TACE chemotherapy regimen has not yet been determined. TH-302 is a hypoxia inducible agent that can be activated in the hypoxic environment induced by TACE. 