A formal interaction test confirmed that the detrimental effect of high IL-17A was amplified in the presence of hyperbilirubinemia (HR = 2.72, 95% CI 1.28-5.75, P = 0.009).<h4>Conclusion</h4>PD-1 inhibitor combined with targeted therapy is safe and feasible in advanced HCC patients with hyperbilirubinemia, although efficacy is inferior to that in patients with normal bilirubin. Here, IL17A is linked to Hyperbilirubinemia.