〔Abstract〕 Objective To evaluate the efficacy and safety of Guben Qingfei Prescription combined with conventional Western medicine in the treatment of patients diagnosed with viral pneumonia by Western medicine and epidemic disease (deficiency of vital qi, damp-heat toxic syndrome) by Traditional Chinese Medicine (TCM). Methods A prospective single-arm trial study was conducted, including 100 patients diagnosed with viral pneumonia by Western medicine and epidemic disease (deficiency of vital qi, damp-heat toxic syndrome) by TCM, who were admitted to Shenzhen Hospital of Traditional Chinese Medicine from January 20, 2023, to January 15, 2024. On the basis of conventional Western medicine treatment, Guben Qingfei Prescription was added for 5 days. The main symptoms TCM syndrome scores and laboratory test indicators were observed and compared before and after treatment. Results After treatment with Guben Qingfei Prescription combined with conventional Western medicine, the hospital stay of the 100 patients was 8 (7, 11) days, with no adverse events or deaths; the TCM syndrome scores for main symptoms such as fever, cough, fatigue, sputum volume, and dyspnea were all lower than those before treatment; white blood cell count, C-reactive protein, erythrocyte sedimentation rate, procalcitonin, and interleukin-6 were all lower than that before treatment, while lymphocyte count was higher than that before treatment, with statistically significant differences (P < 0.05). Conclusion This study found that for patients diagnosed with viral pneumonia by Western medicine and epidemic disease (deficiency of vital qi, damp-heat toxic syndrome) by TCM, Guben Qingfei Prescription combined with conventional Western medicine can effectively alleviate the main clinical symptoms and improve laboratory test indicators with good safety.