ObjectiveTo report the driving and mediating factors of healthcare workers’ anxiety during the COVID-19 pandemic.DesignQualitative indepth interview study.SettingThe Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Participants53 healthcare workers who were or were not diagnosed with COVID-19.ResultsDuring the COVID-19 pandemic, healthcare workers were initially not sufficiently psychologically prepared. Then they suffered from severe anxiety and apprehension during the peak stage, regardless of whether they were infected with SARS-CoV-2 or not. These negative emotions were exacerbated by four drivers, namely infection risk, supplies, isolation and media. As the epidemic gradually came under control, healthcare workers experienced less anxiety from these factors, but became concerned about their low financial status. To reduce anxiety, healthcare workers diverted their attention from the risk of infection through personal entertainment and religious beliefs and focused on treating their patients. Furthermore, assistance from other people, including colleagues, families, friends, patients and society, helped protect healthcare workers from anxiety.ConclusionsPersonal and social support can relieve healthcare workers’ anxiety to some extent during the different stages of an epidemic. Both protective equipment and financial allowance motivate healthcare workers to focus on patient care, although the latter matters more as the epidemic comes under control.