In summary, the systematic bioinformatics analyses in this study showed that NEK2 and its interacting proteins (MAD1L1, CEP250, MAPK1, NDC80, PPP1CA, PPP1R2, NEK11), especially NEK2 key interacting proteins (NDC80 and CEP250), are significantly involved in HCC. This evidence concerns the gene MAPK1 and hepatocellular carcinoma.