Subgroup analysis by cancer type revealed that HHLA2 overexpression was correlated with poor OS in patients with ccRCC (HR = 3.42, 95% CI: 2.39–4.91), GC (HR = 2.03, 95% CI: 1.31–3.16), ICC (HR = 1.77, 95% CI: 1.24–2.53), lung cancer (LC) (HR = 2.14, 95% CI: 1.33–3.44) and other cancer types (HR = 2.08, 95% CI: 1.34–3.24), but not in patients with EOC (HR = 0.52, 95% CI: 0.08–3.56). Here, HHLA2 is linked to intrahepatic cholangiocarcinoma.