Objective Increasing evidence suggests that psychological factors are involved in tumor progression. This study investigated the influence of anxiety and serum catecholamines (CAs) on the prognosis of hepatocellular carcinoma (HCC). Method We enrolled 110 HCC patients who underwent tumor resection at the Affiliated Hospital of Nantong University, China, in this long‐term investigation between 2005 and 2009. We evaluated anxiety using the Hamilton Anxiety Rating Scale (HAMA) and analyzed CA levels using an ELISA kit. We then assessed the association of each of them with overall survival (OS) and time to recurrence (TTR), as well as with other clinical variables. Results The HAMA scores significantly correlated with metastasis (P = 0.015), hepatitis B surface antigens (HBsAg) (P = 0.045), and the tumor‐node‐metastasis stage (P = 0.032), whereas the CA levels also significantly associated with tumor differentiation (P < 0.001). Univariate and multivariate analyses revealed that HAMA scores and CA levels were significant predictors of OS and TTR in HCC patients, with high levels of each being strongly correlated with poor prognosis. Conclusion The HAMA scores and the CA levels were elevated in HCC patients and correlated with OS and TTR, suggesting that they are candidate prognostic markers of HCC.