Objective Investigate the disease uncertainty and psychological distress status of maintenance hemodialysis patients, and explore the correlation between them, so as to provide a basis for improving the mental health level of patients. Methods Using a convenient sampling method, in November 2024, 100 patients in Beijing 3 armour hospital were selected. A general data questionnaire was used to collect patients' baseline data, and the Distress Thermometer (DT) and the Disease Uncertainty Scale were administered to patients to analyze the relationship between the two factors. Results The average score of psychological distress in maintenance hemodialysis patients was 3.55±2.302, with 51% of patients experiencing significant psychological distress. The average score of illness uncertainty was 97.52±23.322. Single-factor variation analysis showed significant differences in caregivers' physical status and differential residence mode (P <0.05). Multiple regression indicated that the degree of disease uncertainty, residence style, and caregiver physical state were the influencing factors of psychological distress (P<0.05). Pearson Correlation analysis showed that levels of disease uncertainty were significantly and positively associated with psychological distress status. Conclusions The levels of disease uncertainty and psychological distress in maintenance hemodialysis patients are not very optimistic, which is related to factors such as caregivers' physical state and residence style, and the two factors are positively correlated. Nursing staff should pay attention to the changes in patients' psychological state, implement personalized psychological nursing, and strengthen health education, so as to effectively improve the mental health status of patients.