Background: Statins are frequently used for the control of hyperlipidemia. Statins have multiple anti-cancer properties and may be associated with lower CRC risks among their users. This study tries to go a step further and explores whether statin use affects the prognosis of curatively resected CRC. Methods: We established a population cohort with patients (age ≥ 40 y) who were diagnosed as having stage I or II CRC from 2004 to 2008 and received curative surgery from the database of Taiwan Cancer Registry. Data of medication prescription and co-morbidities were retrieved from the database of National Health Insurance, Taiwan. Regular statin use was defined as taking statins for > 180 days within the observation period from one year before the cancer diagnosis to one year afterward. The database of National Death Registry was used for survival outcomes. Another similar cohort consisting of patients with hepatocellular carcinoma (HCC) was used for comparison. Results: In total, 10762 patients with CRC were enrolled; 891 (8%) patients were regular stain users, 812 (8%) patients took statins but were not regular users, and 9059 (84%) patients never used statins. Regular statin users, compared to never users, were more likely to be female (p < 0.001), older (p < 0.001), have stage I disease (p < 0.001) and co-morbidities such as diabetes, coronary artery disease, and renal disease. Adjuvant therapy was less frequently administered in regular statin users. In univariate analysis, cancer-specific survival (CSS) of regular stating users was significantly longer than that of never users (5-y CSS, 87% vs. 84%, p = 0.022), but overall survival (OS) was not significantly different (5-y OS, 80% vs. 77%, p = 0.156). In multivariate analysis adjusting for age, gender, stage, adjuvant therapy, co-morbidities, and the use of aspirin, regular stating use was an independent predictor both for better CSS (hazard ratio [HR] 0.72, p < 0.001) and for better OS (HR 0.71, p< 0.001). In contrast, no associations were found between statin use and CSS or OS in the HCC comparison cohort. Conclusions: Regular statin use was associated with better prognosis in CRC patients who received curative therapy. (This study was supported by grants DOH-101-TD-B-111-001 and DOH-102-TD-B-111-001).