R-CHOP chemotherapy has been established as the first-line standard treatment for elderly patients diagnosed with diffuse large B-cell lymphoma. However, an increased risk of Pneumocystis jirovecii pneumonia in diffuse large B-cell lymphoma patients after the rituximab-based chemotherapy has been reported. We describe a case who developed intermittent cough, fever and shortness of breath after five cycles of R-CHOP treatment for diffuse large B-cell lymphoma. A rapid deterioration in patient's respiratory condition prompted us to adopt an aggressive anti- Pneumocystis jirovecii pneumonia strategy that combined the conventional trimethoprim/sulfamethoxazole and another two antimicrobials, caspofungin and clindamycin. This is the first report mentioning the successful treatment of severe Pneumocystis jirovecii pneumonia with a triple-drug regimen in a HIV-uninfected patient. The aim of our report is also to emphasize that early and correct diagnosis of Pneumocystis jirovecii pneumonia in immunocompromised HIV-uninfected patients is very important. Relevant oncologists should be alert to the risk of Pneumocystis jirovecii pneumonia in patients receiving R-CHOP chemotherapy.