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Summary Background/Aims Methods Results Conclusions Patients with hepatocellular cancer (HCC) are vulnerable to psychological distress given a new cancer diagnosis superimposed on pre‐existing chronic liver disease. We aimed to characterise the psychiatric burden in HCC, risk factors for incident diagnosis and treatment patterns over time.Using IQVIA PharMetrics® Plus for Academics—a nationally representative claims database of the commercially insured US population—we identified psychiatric diagnoses and treatment among patients with newly diagnosed HCC. Multivariable logistic regression modelling identified factors associated with psychiatric diagnosis and treatment.Of 11,609 patients with HCC, 2166 (18.6%) had a psychiatric diagnosis after cancer diagnosis with depression (58.3%) and anxiety (53.0%) being most common. Women (aOR 1.33, 95% CI [1.19–1.49]), pre‐existing psychiatric diagnoses (aOR 9.12 [8.08–10.3]) and HCC treatment type (transplant: aOR 2.15 [1.66–2.77]; locoregional therapies: aOR 1.74 [1.52–1.99]; hospice: aOR 2.43 [1.79–3.29]) were significantly associated with psychiatric diagnosis. Female sex, ascites, higher comorbidity and treatment type were associated with incident psychiatric diagnosis. Pharmacotherapy was used in 1392 (64.3%) patients with a psychiatric diagnosis, with antidepressants (46.2%) and anxiolytics (32.8%) being most common. Psychiatric diagnoses increased from 14.8% in 2006–2009 to 21.1% in 2018–2021 (p < 0.001). In almost 20% of patients with pre‐existing psychiatric conditions, therapy was discontinued after HCC diagnosis.Nearly 2 of 10 patients with HCC were diagnosed with a psychiatric condition after cancer diagnosis with unique sociodemographic and clinical risk factors identified. This highlights a risk for increased psychological burden in need of early evaluation and treatment among patients with newly diagnosed HCC. [ABSTRACT FROM AUTHOR]