Richter's syndrome, the development of high-grade non-Hodgkin lymphoma in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), may be triggered by viral infections (eg, Epstein-Barr virus infection). Herein, we report an unusual case of CD5-negative CLL/SLL patient with gastrointestinal mantle cell lymphoma (MCL) and hepatitis B virus infection. CLL/SLL was diagnosed based on lymph node immunohistochemistry and bone marrow pathology. This patient was treated with seven cycles of multi-agent chemotherapy. During treatment, the hepatitis B viruses were activated. Then, after 20 months of antiviral treatment with entecavir, he developed abdominal discomfort and abdominal lymphadenopathy and was diagnosed with MCL based on intestinal biopsy. This work indicates that the hepatitis B virus in patients with CLL/SLL may accelerate the progress or transformation to MCL.