In the present study, the genes expressed in the nontumor liver tissues and tumor liver tissues from the two GEO and TCGA databases were analyzed and filtered to identify a novel set of four-gene signatures (CLEC1B, GYS2, CYP2C8, and EXO1) to diagnose and determine the prognosis of patients with HCC. This evidence concerns the gene CLEC1B and hepatocellular carcinoma.