ObjectiveTo explore the mechanism of postoperative recurrence of hepatocellular carcinoma(HCC) and predicting the candidate drug. MethodsThe differently expressed genes of the human gene expression profiles with 35 postoperative recurrence of HCC tissues and 41 no recurrence of HCC tissues were identified. Then enriched these genes with gene ontology(GO) terms and KEGG pathway, and predicting the candidate drugs for suppress the postoperative recurrence using Connectivity Map(cmap) database. ResultsSeveral pathways such as Focal adhesion and MAPK signaling pathway were found involve in postoperative recurrence of HCC. Moreover, two candidate small molecule drugs(bambuterol and lovastatin) were found may suppress and postoperative recurrence of HCC. ConclusionFocal adhesion and MAPK signaling pathway may involve in the postoperative recurrence of HCC, bambuterol and lovastatin may candidate drugs for treat postoperative recurrence of HCC.