Objective To compare the effects of the 36-item short form health survey (SF-36) and the five-level EuroQol five-dimensional questionnaire(EQ-5D-5L) on the quality of life of patients with advanced schistosomiasis. Methods A total of 125 patients with advanced schistosomiasis were selected from two hospitals in Jiaxing City in 2020, and the general information of the patients was collected, including name, sex, age, and clinical classification of advanced schistosomiasis. The SF-36 and EQ-5D-5L scales were used in questionnaire; investigate the quality of life of patients with advanced schistosomiasis, the reliability and validity of the two scales in evaluating the quality of life of patients with advanced schistosomiasis, and the degree of differentiation in patients with different health levels were compared. The correlation between the scores of the two scales and the factors influencing patient scores were also analyzed. Results The 125 patients with advanced schistosomiasis ranged in age from 47 to 93 years, with an average age of (75.04 ± 7.53) years. There were 46 males (36.80%) and 79 females (63.20%). There were 54 cases (43.20%) of splenomegaly type and 71 cases (56.80%) of ascitic type. The Cronbach’s α coefficient of internal coherence in SF-36 was 0.780 and two factors were extracted by principal component analysis, with a cumulative contribution rate of 70.427%. The Cronbach’s α coefficient of EQ-5D-5L was 0.850 and two factors were extracted by principal component analysis, with a cumulative contribution rate of 85.884%. Among the dimensions of SF-36, the highest average score was on mental health (66.82 ± 7.90), and the lowest scores were on role physical (0) and role emotional (0); the average score of physical component summary (PCS) was(33.85 ± 8.92) and mental health measurement (MCS) was(39.76 ± 4.93), and number of patients with higher MCS score were higher than those with PCS. The average EQ-5D-5L utility index (UI) score was (0.801 ± 0.214). The patients with the dimension of "pain or discomfort" presenting “moderate difficulty, severe difficulty and extreme difficulty” accounted for highest proportion of 24.80%, and the dimension “anxiety or depression” lowest proportion of 5.60%. The average score on visual analogue scale (EQ-VAS) was 66.64 ± 7.85. The age of the patients showed significant influence on the scores of PCS, MCS and EQ-VAS (P < 0.01), but there was no significant difference in the scores of different gender and clinical classification of the patients (P > 0.05). The UI score and EQ-VAS score of those with higher PCS and MCS scores were higher than those with lower PCS and MCS scores (P < 0.01). With the increase of the severity of each dimension of EQ-5D-5L, PCS and MCS scores of patients decreased. PCS was correlated with UI and EQ-VAS scores (r = 0.716, 0.689, P < 0.01), and MCS was correlated with UI and EQ-VAS scores( r = 0.622, 0.544, P < 0.01). Conclusion Both SF-36 and EQ-5D-5L can be used to evaluate quality of life of patients with advanced schistosomiasis, and the assessment outcomes are comparable and complemental. However, as EQ-5D-5L advantages with higher reliability, validity and simpler system structure, thus is more suitable for evaluation of quality of life of patients with advanced schistosomiasis.