LASSO and Cox regression were used to construct a prognostic two-gene (ASF1A and HJURP) model based on H3–H4 histone chaperones for HCC in TCGA-LIHC, which was evaluated in International Cancer Genome Consortium-Liver cancer-RIKEN (ICGC-LIRI) and GSE14520. The gene discussed is ASF1A; the disease is hepatocellular carcinoma.