In summary, we identified GPC3, ACSM3, SPINK1, COL15A1, TP53I3, RRAGD, and CLDN10 as diagnostic immune-related biomarkers with potential clinical utility, which might have the ability to accurately early diagnosis of HCC, enable earlier access to intervention, and improve the clinical outcomes. Here, SPINK1 is linked to hepatocellular carcinoma.