Dyslipidemia is common in patients with chronic kidney disease (CKD), however the relationship between dyslipidemia and mortality in patients with moderate to severe CKD remains controversial. Non-high-density lipoprotein (HDL) cholesterol has been reported to be a more accurate predictor of clinical outcomes than conventional lipid measurements. Hence, the aim of this study was to investigate associations between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3-5. We enrolled 429 pre-dialysis patients with stage 3 to 5 CKD from May 2006 to January 2010. The patients were divided into four groups according to quartiles of non-HDL cholesterol. The patients were followed until death or until January 2020. During a median 11.6 years of follow-up, there were 78 (18.2%) deaths overall and 32 (7.5%) cardiovascular deaths. In adjusted models, the patients in quartile 1 (hazard ratio [HR] 3.368; 95% confidence interval [CI] 1.388-8.176; p = 0.007), quartile 3 (HR 3.666; 95% CI 1.486-9.044; p = 0.005), and quartile 4 (HR 2.868; 95% CI 1.136-7.240; p = 0.026) of non-HDL cholesterol had a higher risk of overall mortality (vs. quartile 2). In addition, the patients in quartile 1 (HR 19.503; 95% CI 2.185-174.0925 p = 0.008), quartile 3 (HR 28.702; 95% CI 2.990-275.559; p = 0.004), and quartile 4 (HR 11.136; 95% CI 1.126-110.108; p = 0.039) had a higher risk of cardiovascular mortality (vs. quartile 2). Our study showed a U-shaped relationship between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3-5. Assessing non-HDL cholesterol may help to identify subjects at high-risk of adverse outcomes.