The employees of Taiwan are getting higher work stresses from highly competitive labor market, so that their job satisfactions are affected. The aim of current study is to investigate the effect of work stress on job satisfaction. In addition, the exploration of the moderating effect of the big five personality traits is the purpose of this study as well. Based on the data surveyed and collected from 187 employees of medical centers across different regions in Taiwan, this study presents work stress as a predictor of job satisfaction, and the big five personality traits as moderators of the above relationship. The hierarchical regression analysis is the main analysis method to examine the hypotheses. The results show that: 1.There is a negative effect of work stress on job satisfaction. 2.The conscientiousness and extraversion personality traits have moderating effects between work stress and job satisfaction. The employees with higher degree of conscientiousness or extraversion personality traits, their negative effects between work stress and job satisfaction are weaker. According to the results, the theoretical contributions, practical implications and future research directions are discussed.