BACKGROUND AND OBJECTIVE: Bladder cancer and emotional stress are both common physiologic problems, with few published studies and a lack of studies with large samples discussing their association. The aim of this study was to investigate the association between bladder cancer and emotional stress. RESEARCH METHODS: We used data from the U.S. National Health and Nutrition Examination Survey (NHANES) database for the period 2005 to 2020 and the Bladder Cancer Database from Shanghai Tenth People's Hospital of Tongji University. The above two databases were used for two independent cross-sectional studies, respectively. We adopted the method of multivariate logistic regression to analyze the relationship between the occurrence of bladder cancer and depression, as well as the relationship between the recurrence of bladder cancer and emotional stress. RESULTS: Based on the NHANES database, a total of 23,801 participants were enrolled in our study, including 100 participants diagnosed with bladder cancer and 23,701 participants not diagnosed with bladder cancer. After adjustment for covariates, there was a significant positive association between bladder cancer and mild depression (OR: 2.43, 95% CI: 1.41, 4.00). There was a significant positive association between recurrence of bladder cancer and general depression (OR: 2.16, 95% CI: 1.20, 3.88) among 303 bladder cancer patients in the Chinese database. CONCLUSION: This study reveals a strong association between bladder cancer and emotional stress, with patients with bladder cancer having a significant risk of depression and elevated emotional stress potentially associated with bladder cancer recurrence.