Hepatocellular carcinoma (HCC) is considered as the leading killer disease in the world. So far most of the diagnosis of HCC is mainly established on imaging and biopsy. As sequencing technology is developing quite fast, and it has already been widely applied in the medical area, such as cancer diagnosis. In this article, GSE121248, GSE76427 and GSE60502 datasets were chosen to analyze and screen key genes which could affect the development of liver cancer through the bioinformatics method. The results showed up regulated genes mainly reside in cell division, nucleus, protein binding pathway, and down regulated genes are mostly located in the Oxidation-reduction process, Extracellular region, Heme binding, Metabolic pathway. Secondly, hub gene analysis indicated there were twelve critical hub genes found: RFC4, RACGAP1, CCNB2, CDC20, UBE2C, PTTG1, AURKA, PRC1, NCAPG, CDKN3, TOP2A, KIF20A, AURKA and CDKN3. By applying bioinformatic measures , the genes associated with hepatocellular carcinoma can be efficiently analyzed, that would provide invaluable information for translational studies.