Objectives In modern professional life, mental health prevention and promotion have become a major challenge for decision-makers. Devising appropriate actions requires better understanding the role played by each work-related psychosocial factor (WPSF). The objective of this study was to present a relevant tool to hierarchise WPSFs that jointly takes into account their importance (impact on mental health) and their prevalence (the proportion of the population exposed to WPSF). Design A cross-sectional study was conducted in March 2018 among 3200 French workers which are representative of the French working population. Setting France. Participants Individuals aged 18–80 years who declared currently having a job (even a part-time job) whatever their occupation or status (employee or self-employed) were eligible. We excluded students, unemployed individuals, housewives/husbands and retired people. The mental health level was assessed using the General Health Questionnaire-28 and 44 items were gathered from theoretical models of WPSFs. We assessed two distinct multivariate methods for calculating WPSF importance: (1) weifila (weighted first last) method in a linear regression context and (2) random forests in a non-linear context. Both methods were adjusted on individual, health and job characteristics. Results The WPSF rankings obtained with the two methods to calculate importance are strongly consistent with each other (correlation coefficient=0.88). We highlighted nine WPSFs that are ranked high by both methods. In particular, irrespective of the chosen method, lack of communication, lack of social and hierarchy support and personal–professional life imbalance, emotional demands at work and dissatisfaction with the compensation received came out as top-ranking WPSFs. Conclusions A total of nine WPSFs were identified as key for decision-making. The easy-to-use tools we propose can help decision-makers identify priority WPSFs and design effective strategies to promote mental health in the workplace.