Background: Reports had found an association between B cell non-Hodgkin lymphomas (NHL) and Hepatitis C virus (HCV) infection. However, data on acute exacerbation and reactivation of chronic HCV infection following chemotherapy are very limited. We studied the efficacy of ribavirin to prevent hepatitis reactivation in HCV-infected patients treated for NHL. Methods: This study was carried out at Hematology and Medical Oncology unit, Internal Medicine Department, Zagazig University Hospitals and it included 57 patients with B-cell NHL who were naive to chemotherapy, among them 24 patients were positive for HCV antibody and 33 patients were negative for HCV (group C). The HCV infected group was subdivided into 11 patients who received ribavirin (group A) and 13 patients did not receive ribavirin (group B)and routine investigations for NHL were done, HCV RNA was measured for HCV infected patients before and after the end of chemotherapy. Results: HCV infection occurred in 42% of patients with B cell NHL. Acute hepatic enzyme exacerbation occurred in 8 (14%) of all patients with the highest percentage was 29.2 % among HCV infected patients (7/24), while only one patient (3%) in the HCV negative group (P = 0.007). Among the 24 NHL patients with HCV positivity, we compared group A and group B during chemotherapy as regards to hepatic enzyme flare, it was (27% and 30%, respectively, P = 0.6). Five (20.8%) of 24 NHL patients with HCV positivity were developed HCV PCR reactivation. Conclusions: The frequency of HCV infection in patients with B cell NHL was higher than in the general population and acute exacerbation and reactivation of chronic HCV infection occurred in a sizeable subset of patients with NHL during chemotherapy, However the use of ribavirin did not decrease hepatic enzyme flare or HCV PCR reactivation during chemotherapy.