The present article tries to gather empirical evidence for the moderating role of occupational self-efficacy beliefs between job satisfaction and specific responses to stress such as irritation at work. A multi-occupational sample of 386 subjects participated in this study, 47.1% women and 52.9% men. The mean age was 38 years old (s.d. 12.03), all of them in an active situation when filling in the following questionnaires: The Irritation Scale, the Job Descriptive Index, and the Occupational Self-Efficacy Scale. Correlation analyses, analyses of variance and regression analyses were carried through. Results obtained through correlation analyses confirmed a positive relation between occupational self-efficacy and job satisfaction (dimensions work itself, supervision, and promotion, p < 0.01), and a negative relation between emotional irritation and occupational self-efficacy (p < 0.01). Besides, analyses of variance and regression analyses confirmed that among the subjects with lower levels of job satisfaction, those with higher self-efficacy showed lower levels of stress, thus, confirming the moderating role of occupational self-efficacy on work stress experience. Therefore, an important conclusion or implication of the results is the confirmation of the occupational self-efficacy as a moderator between the satisfaction and the experience of irritation at work.