Verruca vulgaris is always stubborn to treat. We applied a new combined therapy of local recombinant human interferon alpha 1b (rhIFNα1b) injection plus acupuncture on verruca vulgaris recently to evaluate the efficacy and safety of the combined therapy. The retrospective study was conducted in The First Hospital of China Medical University from 2018 to 2020. Patients with verruca vulgaris were included. Combined therapy with local rhIFNα1b injection plus acupuncture was set as treatment group, rhIFNα1b injection and carbon dioxide (CO₂) laser were set as control groups. A total of 2415 patients were included in the study. The cure rates were 81.85%, 85.93%, and 100% in combined group, rhIFNα1b group, and CO₂ laser group, separately. All lesions cured in combined group were located on hands or feet, while majority of lesions cured in other groups were located on other sites. For patients with medium/big single lesion or 6–9 lesions, less treatment times were needed in combined group than rhIFNα1b group. For patients with small single, two to five or more than ten lesions, the treatment times of combined group and rhIFNα1b group were comparable. All patients complained of pain in varying degrees when local injection or laser irradiation. Compared with CO₂ laser group, more fever, less swelling or scar was reported in combined group. In conclusion, combined therapy of local rhIFNα1b plus acupuncture was beneficial for verruca vulgaris with limited adverse effects. The therapy was more acceptable by younger female patients with verruca vulgaris.