Nursing is recognized as a stressful occupation and has indicated a probable high prevalence of distress. The purpose of this study was to identify the degree of job strain and to investigate the association between job strain and the minor psychiatric disorder in hospital nurses. A total of 907 registered nurses were recruited for this study via stratified random sampling from hospitals in Kaohsiung, Taiwan. Each participant was requested to answer a structured questionnaire anonymously and a 98.1% response rate was achieved. The Job Strain Questionnaire was used to measure job strain. The minor psychiatric disorder was measured by the Chinese Health Questionnaire, and a cut-off score of 4 or more was used to identify which subjects had minor psychiatric disorder. Results indicated that 24.5% of the nurses were in the high strain group and that those who were unmarried, had a lack of social support, and those with shift work were the most susceptible to high job strain. A total of 443 (48.8%) respondents were identified as having minor psychiatric disorder. Multiple logistic regression revealed that high job strain, poor social support, and poor self-perceived health were the significant factors for nurses to have minor psychiatric disorder. These findings suggested that the best way to decrease the prevalence of psychological distress of nurses might focus on organizational attempts to reduce work stress and to develop effective health promotion programs and give more assistance to nurses who have a managerial role.