Background & Aims Treatment of hepatocellular carcinoma (HCC) with immune checkpoint inhibitors (ICIs) is associated with the development of hepatic immune‐related adverse events (HIRAEs). We aimed to evaluate the role of baseline hepatic tumour burden, measured with the tumour burden score (TBS), in the development of HIRAEs and survival. Methods We conducted a retrospective observational cohort study on 93 patients treated with ICIs at IRCCS Humanitas Research Hospital, of which 42 for advanced HCC (Cohort 1) and 51 for non‐HCC cancers with liver metastases developed prior to immunotherapy initiation (Cohort 2). We assessed the baseline tumour burden using TBS: TBS2 = (maximum tumour diameter)2 + (number of liver lesions)2. Results In the cohort of patients with HCC, 18 patients (42.86%) developed any grade (G) HIRAEs, of which eight (19.05%) were G ≥ 2. Patients who developed any‐grade HIRAEs had a higher median TBS compared to patients with no HIRAEs (10.95 vs 5.85; P = .11). Baseline TBS correlated with the development of any‐grade HIRAEs with marginal statistical significance (odds ratio [OR] 1.37, P = .08). Median OS was not influenced by TBS or by the development of HIRAEs. In the cohort of non‐HCC patients, 18 patients (35.29%) developed any‐grade HIRAEs, of which three (5.88%) were G ≥ 2. Baseline TBS did not correlate with the development of any‐grade HIRAEs (OR 1.01), and median OS was not influenced by TBS or HIRAEs. Conclusions Despite the limited sample size and the absence of statistical significance, our study suggested a possible association between baseline TBS and the development of any‐grade HIRAEs in the HCC cohort. Future evaluation of larger cohorts is needed to corroborate these findings.