Objective To observe and compare the efficacy and safety of different doses of sodium thiosulfate for the treatment of pruritus in maintenance hemodialysis (MHD) patients.  Methods  A total of 126 MHD patients with pruritus from 11 general hospitals in Shanghai during January 2020 to December 2022 were included in this study. They were randomly divided into three groups. The dose of sodium thiosulfate was 1.92g in group 1, 3.20g in group 2, and 4.48g in group 3. The treatment period lasted 8 weeks. Clinical effects and safety including pruritus score, biochemical indicators and adverse reactions were observed and compared between the groups.  Results Compared with the pruritus scores 5 days before the treatment and 8 weeks after the treatment, the decreases of pruritus score were 18.6±1.91 to 12.8±3.03, 19.0±2.80 to 11.3±3.40 and 19.6±3.64 to 10.9±3.75 in group 1 (n=72), 2 (n=79) and 3 (n=75) respectively; the extent of decrease were statistically significant among the 3 groups (F=2.735, P=0.046), and the extent of score decrease was greater in group 3 than in group 1 (score difference=-1.352, 95% CI: -2.645～-0.060, P=0.041). No adverse reactions such as allergic reactions, rash and hypotension were found during the observation period. Multivariate analysis showed that compared with group 1 the slope of pruritus score 5 days before the treatment and 8 weeks after the treatment in group 3 showed β= -1.650 (95% CI: -3.046～-0.253, P=0.021).  Conclusion  Sodium thiosulfate can effectively relieve the pruritus symptoms in MHD patients, and the effect is enhanced with increase of the dose. No obvious adverse reactions were found. This treatment is therefore safe and effective.