Objective To compare the difference of mortality risk between patients undergoing nocturnal hemodialysis (NHD) and conventional hemodialysis (CHD) and to explore the related factors of mortality. Methods The study cohort comprised the maintenance hemodialysis patients receiving either NHD (n=111) or CHD (n=722) in Changzheng Hospital of Second Military Medical University from Feb. 2009 to Feb. 2017. The demographic information, clinical characteristics, survival status, causes of death and laboratory examination indexes were obtained from hemodialysis management system. The urea clearance index (Kt/V), hemoglobin, blood phosphorus concentration and mortality were compared between NHD and CHD patients. The multivariate-adjusted Cox model was used to analyze the mortality risk of all patients. Results Compared with the patients receiving CHD, the proportion of male was more in the NHD group, and the baseline age was younger (P<0.01) and baseline dialysis vintage was longer (P<0.01). There was no significant difference in incidences of primary disease and comorbidities, or laboratory examination results. Compared with the CHD group, the levels of Kt/V and hemoglobin in the NHD group were significantly higher (P<0.01), and the blood phosphorus concentration was significantly lower (P<0.05). Mortality in the NHD and CHD groups was 3.5 per 100 patients-years and 6.2 per 100 patients-years, respectively. After the adjustment by baseline age, dialysis vintage, gender, and comorbidities, Cox model analysis showed that the mortality risk in the NHD group was lower than in the CHD group (HR=0.67, 95%CI:0.39-1.00, P=0.05). Subgroup analysis showed NHD was of more survival benefit for male (P<0.05), non-diabetic patients (P=0.05) and patients with conventional dialysis vintage >3 years (P<0.05). Conclusion NHD can effectively increase the solute clearance, improve anemia and calcium and phosphate metabolism, and thus reduce the mortality risk of maintenance hemodialysis patients.