Background: Hepatitis C virus (HCV) infection is one of the most common blood-borne infection in the world, and with an estimated to be infected more than 880,000 people in Japan. Little is known about the changes of HCV status during chemotherapy and the influence of HCV infection on toxicity of chemotherapy. Methods: We reviewed all patients diagnosed with colorectal cancer in our institution between 2001 and 2012 who had been screened for HCV infection by testing for anti-HCV antibody and identified 77 HCV-infected patients. We retrospectively analyzed the change in HCV load and the toxicities of chemotherapy in these patients. Results: Twenty-four of the 77 HCV-infected patients with colorectal cancer had received chemotherapy.The median age was 66 years (range: 42-80 years). Four patients had liver cirrhosis at the initiation of chemotherapy. The remaining 20 patients were diagnosed with chronic hepatitis, and their liver function tests and complete blood cell counts at baseline were normal. First-line chemotherapy included 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) (n = 6), S-1 and irinotecan (IRIS) (n = 1), tegafur-uracil (n = 14), capecitabine (n = 1), capecitabine and oxaliplatin (XELOX) (n = 2).Serum HCV-RNA levels both before and after chemotherapy were evaluated in 10 patients, and the median serum HCV-RNA level before and after chemotherapy was 4.0 and 3.05 logIU/ml, respectively. Transaminase levels were elevated during chemotherapy in 2 patients. There were no patients suffered from grade 3-4 neutropenia or febrile neutropenia. Conclusions: This study indicates that chemotherapy can be safely performed in HCV-infected patients with colorectal cancer without change in HCV load.