Patients with severe mental illnesses (SMI) were at high risk of infection during Coronavirus Diseases 2019 (COVID-19) pandemic. This study examined hospitalized SMI patients’ attitude and knowledge towards the COVID-19 infection. A cross-sectional survey was conducted in five psychiatric hospitals located in Gansu province, the most economically underdeveloped area in China. Patients’ attitude towards preventive measures and knowledge of COVID-19 were measured by a self-report questionnaire. A total of 925 hospitalized patients with SMI were recruited. Of them, 84.8% (95%CI: 82.4%–87.1%) had positive attitudes towards preventive measures of the COVID-19 outbreak. Being married (OR: 1.55, 95%CI: 1.05–2.30) and a higher educational level (OR: 1.63, 95%CI: 1.12–2.38) were independently associated with positive attitudes towards COVID-19 preventive measures, whereas higher educational level was associated with better knowledge of the COVID-19 outbreak (β: 0.231, P < 0.001). Patients mainly received COVID-19 relevant knowledge from public media (58.9%), followed by their clinicians (33.2%). Most hospitalized SMI patients in economically underdeveloped areas in China showed positive attitudes towards COVID-19 preventive measures. However, public health education on COVID-19 relevant knowledge by mental health professionals was inadequate to reduce the risk of transmission and infection.