Objective To evaluate the clinical efficacy and safety of hydroxychloroquine sulfate combined with azithromycin in the treatment of refractory common coronavirus disease 2019 (COVID-19) patients. Methods The clinical data of 11 refractory common COVID-19 patients, who were admitted to Guanggu Branch of Maternity and Child Healthcare Hospital of Hubei Province from Mar. 22 to 25, 2020, were retrospectively collected. The patients all received combined treatment regimens:hydroxychloroquine sulfate orally 200 mg three times daily for 7 days; and azithromycin orally 500 mg once daily on day 1 and then 250 mg once daily from day 2 to day 4. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test of throat swab was performed once daily from day 4 to day 10 after combined administration, and the blood routine and other laboratory indicators were tested within 3 days before administration and on the 8th days after administration. Results All the 11 patients had common COVID-19, seven of them were consistently positive for SARS-CoV-2 nucleic acid test, and four were positive again after negative results. The average course of disease of 11 patients before combined administration was 50.2 days. The treatment process was uneventful. Zero case of SARS-CoV-2 nucleic acid test result turned negative on day 4 after administration, two cases on day 5, two cases on day 6, two cases on day 7, one case on day 8 and one case on day 9. No patients progressed to severe or critical illness, and no severe side effects were found. Conclusion Hydroxychloroquine sulfate combined with azithromycin is safe and effective in the treatment of refractory common COVID-19 patients who have failed in other treatments and are consistently positive for SARS-CoV-2 nucleic acid.