The purpose of this study was to examine knowledge, professional quality of life, and practices among nurses during the coronavirus disease 2019 (COVID-19) pandemic and explore factors associated with nurses’ practice. A total of 167 nurses were recruited from 4 general hospitals for this cross-sectional study, which was conducted from June to July 2021. Using SPSS/WIN 22, the collected data were analyzed using descriptive statistics, t-tests, analysis of variance, Pearson’s correlation coefficients, and hierarchical multiple regression analysis. The mean age of the participants was 31.43, and the sample comprised 144 women (86.2%) and 23 men (13.8%). The results indicated that practice was negatively correlated with burnout (r = -.18, p = .017). The regression model explained 24.1% of the variance. For general characteristics in Model 1, education on COVID-19 management (β = .18, p = .014) was the factor most associated with nurses’ practice. In Model 2, with professional quality of life added, burnout (β = -.21, p = .003) was the only influential factor. These results highlight the need to establish an effective prevention system for infectious diseases such as COVID-19, including education programs pertinent to the prevention and management of infection that improve the modifiable predictors of nurses’ practice—education and burnout.