The clinical features and outcome of 25 previously untreated aggressive non-Hodgidn's lymphoma (NHL) patients with hepatitis C virus (HCV) infection were evaluated retrospectively. The patients included 18 males and 7 females with a median age of 66 years. The median observation period for survivors was 32 months. Although there were no patients with hepatocellular carcinoma during the follow-up period, 7 patients had cirrhosis (LC) at the initiation of therapy for NHL. Seventeen patients (68%) had initial extranodal involvement including 2 cases with liver involvement. The 5-year overall survival (OS) rate in the whole group was 46%, and the 5-year relapse-free survival (RFS) rate of patients with complete response (CR) was 48%. Patients with non-cirrhosis (n = 18) showed better OS (P = 0.04) compared with patients with LC (n = 7) and 5-year OS rates were 55 and 21%, respectively. Fourteen patients died in the whole group; 4 of NHL and 2 of liver failure in the LC group and 8 of NHL in the non-cirrhotic group. Among the latter 8 patients, cumulative dose (CD) of doxorubicin (ADR) and cyclophosphamide (CPA) were significantly lower than those of survivors with non-cirrhosis. In conclusion, patients with HCV-positive aggressive NHL have a similar prognosis as HCV-negative aggressive NHL. In non-cirrhotic patients, attention should be paid to the CD of drugs required to cure the aggressive NHL.