The spread of COVID-19 is accelerating. At present, there is no specific antiviral drugs for COVID-19 outbreak. This is a multicenter retrospective cohort study of patients with laboratory-confirmed COVID-19 infection pneumonia from 3 hospitals in Hubei and Guangdong province, 141 adults (aged ≥18 years) without ventilation were included. Combined group patients were given Arbidol and IFN-α2b, monotherapy group patients inhaled IFN-α2b for 10-14 days. Of 141 COVID-19 patients, baseline clinical and laboratory characteristics were similar between combined group and monotherapy group, that 30% of the patients leucocytes counts were below the normal range and 36.4% of the patients experienced lymphocytopenia. The duration of viral RNA of respiratory tract in the monotherapy group was not longer than that in the combined therapy group. There was no significant differences between two groups. The absorption of pneumonia in the combined group was faster than that in the monotherapy group. We inferred that Arbidol/IFN - 2b therapy can be used as an effective method to improve the COVID-19 pneumonia of mild patients, although it helpless with accelerating the virus clearance. These results should be verified in a larger prospective randomized environment.