Based on the four‐stage design in this study, we finally focused eight autoantibodies against RUNX1T1, RAD23A, CAST, PRKCZ, SF3B3, SARS, DUSP6, and PAIP1 as biomarkers for HCC detection, which were screened out by different experimental techniques and confirmed in a few independent cohorts. The gene discussed is CAST; the disease is hepatocellular carcinoma.