The associations between dietary fat intakes and the risk of colorectal cancer have been examined in many epidemiological studies, but the results have remained inconsistent. This study aimed to examine the associations of total fat and fatty acid intakes with the risk of colorectal cancer in Guangzhou, China. A case–control study was carried out between July 2010 and May 2012 in Guangzhou, China. Four hundred and eighty-nine consecutively recruited colorectal cancer cases were frequency matched to 976 controls by age (5-year interval) and sex. A validated food frequency questionnaire was used to collect dietary information by face-to-face interviews. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The total fat intake was not related to the risk of colorectal cancer, with an OR (95% CI) of 0.95 (0.68–1.32) comparing the highest with the lowest quartiles. Intakes of saturated fat, monounsaturated fat, and n-6 polyunsaturated fat were also not associated with the risk of colorectal cancer. However, a significant inverse association was found between total n-3 polyunsaturated fat, α-linolenic acid, and long-chain n-3 polyunsaturated fat consumption and the risk of colorectal cancer. The adjusted ORs of the highest versus the lowest quartile were 0.45 (95% CI=0.32–0.64, Ptrend<0.01) for total n-3 polyunsaturated fat, 0.54 (95% CI=0.38–0.76, Ptrend<0.01) for α-linolenic acid, and 0.58 (95% CI=0.41–0.82, Ptrend<0.01) for long-chain n-3 polyunsaturated fat. This study suggested that total fat, saturated fat, monounsaturated fat, and n-6 polyunsaturated fat intakes were not related to the risk of colorectal cancer. However, increased consumption of n-3 polyunsaturated fat might reduce the risk.