Chloroquine (CQ) and its derivative, hydroxychloroquine (HCQ), have attracted wide attention for treating coronavirus disease 2019 (COVID-19). However, conflicting outcomes have been found in COVID-19 clinical trials after treatment with CQ or HCQ. To date, it remains uncertain whether CQ and HCQ are beneficial antiviral drugs for combating COVID-19. We performed a systematic review to depict the efficacy of CQ or HCQ for the treatment of COVID-19. The guidelines of PRISMA were used to conduct this systematic review. We searched through articles from PubMed, Web of Science and other sources that were published from 1 January 2020 to 31 October 2020. The search terms included combinations of human COVID-19, CQ, and HCQ. Eleven qualitative articles comprising of four clinical trials and seven observation studies were utilized in our systematic review. The analysis shows that CQ and HCQ do not have efficacy in treatment of patients with severe COVID-19. In addition, CQ and HCQ have caused life-threatening adverse reactions which included cardiac arrest, electrocardiogram modification, and QTc prolongation, particularly during the treatment of patients with severe COVID-19. Our systematic review suggested that CQ and HCQ are not beneficial antiviral drugs for curing patients with severe COVID-19. The treatment effect of CQ and HCQ is not only null but also causes serious side effects, which may cause potential cardiotoxicity in severe COVID-19 patients.