Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world. Hypoxia is closely related to the occurrence and development of HCC. The researches on hypoxia, hypoxia markers and hypoxia-induced tumor neovascularization in HCC have great significance for clinical diagnosis and treatment. Here, the authors address the action mechanisms of hypoxia inducible factors, matrix metalloproteinases, high mobility group protein 1, autophagy gene Beclin-1, neuroglobin, cytoglobin and microRNAs (miRNAs) in HCC.