Nonalcoholic fatty liver disease (NAFLD) is known to be associated with an increased risk of colorectal cancer (CRC). However, the relationship between NAFLD and the prognosis of CRC remains unclear. The primary objective of this study was to evaluate the overall survival (OS) and disease-free survival (DFS) rates in patients with CRC and the secondary objective was to compare clinicopathologic variables which were stratified by NAFLD. We performed a large cohort study of 1314 patients who were first diagnosed with CRC between January 2006 and April 2011. Postoperative follow-up data were collected from out-patient medical records, telephone consultations, and social security death indices. The Kaplan-Meier method was used to calculate the cumulative survival rate. Clinicopathologic variables were analyzed by univariate analysis and multivariate analysis through a Cox proportional hazard regression model. The mean follow-up time was 52.7 ± 25.3 months. Upon baseline comparison, the NAFLD group had significantly higher values of body mass index, triglycerides, and uric acid and significantly lower values of high-density lipoprotein, compared with the non-NAFLD group (P < 0.05 for all). There were no significant differences between the 2 groups with regard to tumor location, TNM staging, tumor differentiation, carcinoembryonic antigen, and vascular invasion. The cumulative 1-, 3-, and 5-year OS rates were 96.1%, 85.2%, and 80.6%, respectively, in the NAFLD group, which were statistically significantly higher than the OS rates of 91.6%, 76.2%, and 67.8%, respectively, in the non-NAFLD group (P = 0.075, P = 0.002, P = 0.030, respectively). There was no difference in DFS rates between the CRC patients with and without NAFLD (P = 0.267). Multivariate analysis showed that the presence of NAFLD was an independent negative risk factor for OS after adjusting for clinicopathologic covariates (hazard ratio = 0.593; 95% confidence interval 0.442, 0.921; P = 0.020), but not for DFS (P = 0.270). NAFLD may play a protective role in OS for CRC patients. Further studies are needed to elucidate the molecular mechanisms of putative protective effects in CRC patients with NAFLD.