Here, we selected ICOS rs4404254 T>C, rs10932029 T>C, CD28 rs3116496 T>C and CD80 rs7628626 C>A polymorphisms and carried out a hospital-based case–control study to explore the potential association of ICOS, CD28 and CD80 SNPs with the risk of HCC. Here, CD80 is linked to hepatocellular carcinoma.