This study evaluated the association of the serum total cholesterol to high-density lipoprotein cholesterol ratio (TC/HDL-C) with mortality in incident peritoneal dialysis (PD) patients. We performed a multi-center, prospective cohort study of 630 incident PD patients from 2008 to 2015 in Korea. Participants were stratified into quintiles according to baseline TC, HDL-C, LDL-C and TC/HDL-C. The association between mortality and each lipid profile was evaluated using multivariate Cox regression analysis. During a median follow-up period of 70.3 ± 25.2 months, 185 deaths were recorded. The highest TC/HDL-C group had the highest body mass index, percentage of diabetes and serum albumin level. Multivariate analysis demonstrated that the highest quintile of TC/HDL-C was associated with increased risk of all-cause mortality (hazard ratio 1.69, 95% confidence interval 1.04-2.76; = 0.036), whereas TC, HDL-C and LDL-C were not associated with mortality. Linear regression analysis showed a positive correlation between TC/HDL-C and body mass index. Increased serum TC/HDL-C was an independent risk factor for mortality in the subgroup of old age, female, cardiovascular disease and low HDL-C. The single lipid marker of TC or HDL-C was not able to predict mortality in PD patients. However, increased serum TC/HDL-C was independently associated with all-cause mortality in PD patients.