Objective: This study aims to investigate the adverse reactions and risk factors associated with toripalimab in the treatment of urothelial carcinoma. Methods: The clinical data of 63 patients with urothelial carcinoma who received toripalimab treatment in our hospital from June 2021 to January 2025 were retrospectively analyzed. Patient data, including baseline characteristics (age, gender, Eastern Cooperative Oncology Group [(ECOG] score, comorbidities), treatment history (chemotherapy, radiotherapy), and adverse reactions, were selected through the hospital’s electronic medical record system. Results: Among the 63 patients, 49 (77.78%) experienced toripalimab-related adverse reactions, with skin rash occurring most frequently. Univariate analysis showed that age, comorbidities such as hypertension, diabetes, and bronchial asthma, as well as the use of combined radiotherapy and chemotherapy, were significantly associated with toripalimab-related adverse reactions (all P < 0.05). Multivariate logistic regression analysis revealed that combined chemotherapy was an independent risk factor for toripalimab-related adverse reactions (P < 0.05). Conclusion: Immune-related adverse reactions observed during toripalimab treatment for urothelial carcinoma include skin rash, elevated transaminase levels, abnormal renal function, anemia, etc. Factors influencing these reactions include age, underlying diseases, and combined radiotherapy and chemotherapy, among which combined chemotherapy is an independent risk factor for adverse reactions. When using toripalimab in clinical practice, it is essential to follow the approved indications on the label, monitor patients for adverse reactions during treatment, and intervene effectively to ensure patient safety.