Abstract Background Hepatitis C virus (HCV)-infected patients with chronic kidney disease (CKD) have rarely been studied because they rarely accept interferon-based therapy (IBT) and have been difficult to follow up. We investigated long-term outcomes of IBT on the population. Methods This population-based cohort study used the Taiwan National Health Insurance Research Database as its data source. HCV patients diagnosed with CKD between Jan. 1, 2003, and Dec. 31, 2013, were selected. They were then divided into two groups based on whether they had undergone IBT. All-cause mortality, acute myocardial infarction (AMI), ischemic stroke (IS), hemorrhagic stroke, and new-onset dialysis were evaluated using a Cox proportional hazard regression analysis after propensity score matching. Results We enrolled 9872 HCV patients with CKD: 1684 patients in the treated cohort and 8188 patients in the untreated cohort. The annual incidence of all-cause mortality (19.00 vs. 42.89 events per 1000 person-years; p < 0.001) and the incidences of hemorrhagic stroke (1.21 vs. 4.19 events per 1000 person-years; p = 0.006) were lower in the treated cohort. New-onset dialysis was also lower in the treated cohort (aHR: 0.31; 95% CI: 0.20–0.48; p < 0.001). Conclusion Antiviral therapy might provide protective benefits on all-cause mortality, hemorrhagic stroke, and new-onset dialysis in HCV-infected patients with CKD.