Abstract:Background and Aims: Hepatocellular carcinoma (HCC) is characterized by a high recurrence rate and unsatisfactory long-term outcomes after curative treatment. With the development of the bio-psycho-social model, the role of psychological factors in cancer prognosis has gained increasing attention. However, prospective evidence regarding the impact of preoperative anxiety and depression on survival in HCC remains limited. This study aimed to evaluate their association with long-term outcomes after curative treatment. Methods: This single-center prospective cohort study consecutively enrolled 213 HCC patients who underwent curative resection or ablation in 2019. Preoperative psychological status was assessed using the Zung Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). Overall survival (OS) was the primary endpoint, while disease-free survival (DFS) was the secondary endpoint. Survival analyses were performed using the Kaplan-Meier method and Cox regression models. Results: The prevalence of preoperative anxiety and depression was 37.6% and 31.0%, respectively, with 45.1% of patients exhibiting at least one condition. Patients with anxiety or depression had significantly worse DFS and OS (both P<0.05). In multivariable analysis, neither anxiety nor depression alone was independently associated with outcomes. However, the combined variable ("anxiety or depression") independently predicted poorer DFS (HR=1.589, P=0.003) and OS (HR=1.844, P<0.001). CNLC stage, surgical approach, and microvascular invasion were also identified as independent prognostic factors. Conclusion: Preoperative psychological distress is common in HCC patients and is associated with unfavorable long-term outcomes. A composite assessment of anxiety and depression provides greater prognostic value than individual symptoms, supporting the integration of psychological screening into perioperative management.