Objective To investigate the COVID-19 knowledge in nurses. Methods A questionnaire was developed to investigate the basic knowledge and protection knowledge of COVID-19 in nurses in two tertiary general hospitals in Hunan Province. Results The total average score of COVID-19 was 56.74±10.85,of which average score of basic knowledge was 25.93±6.39 and prevention knowledge was 30.82±6.51 in 3 119 nurses. Multiple linear regression analysis showed that hospital level,professional title,educational level,gender,and department were the influential factors of knowledge,which could explain 46.0% variation. Conclusion Nurses’ knowledge level about COVID-19 is relatively low and training is urgently needed. The training should particularly target the nurses with male gender,low educational level and professional title. Those who do not work in ICU should also be trained. The COVID-19 prevention and control training program should be improved to increase the program effects.