BackgroundAdrenal insufficiency (AI) is a rare, but potentially serious adverse event associated with immune checkpoint inhibitors (ICIs). This study aims to examine the incidence, clinical features and the clinical correlation between occurrence of AI and efficacy in primary liver cancer (PLC) patients treated with ICIs; and to evaluate the significance of the continuation of ICIs treatment in PLC patients who developed AI. MethodsBetween January 2020 and March 2022, 47 PLC patients with ICIs-associated AI (AI cohort) were screened from Zhongshan Hospital, Fudan university, a general hospital in China. Between December 2019 and August 2021, 419 PLC patients who were treated with ICIs were reviewed to identify those without immune- associated adverse events (irAEs) (control cohort). Clinical features and outcomes of the PLC patients from the two cohorts were compared. ResultsTotally, 47 PLC patients with AI (AI cohort) and 63 PLC patients without irAEs (control cohort) were included. The incidence of grades 3–4 of AI and all irAEs were 40.4 % and 48.9 %, respectively. The median three-year survival was significantly longer in the AI cohort than that in the control cohort (26.3 months (95 % CI: 18.9––33.5) vs.16.1 months (95 % CI:10.4––21.7); p = 0.021). Multivariable cox proportional hazards regression model showed that the development of AI remained significantly associated with improved overall survival (HR = 0.561; p = 0.033) in the adjusted regression analysis. ConclusionThe current study demonstrated that PLC patients undergoing ICIs therapy and developing AI after ICIs treatment had favorable survival outcomes compared to those without irAEs.