Purpose The study estimates the prevalence of probable psychiatric disorder in the working population, determines the proportion of people presenting a probable psychiatric disorder among people exposed to work-related psychosocial risk factors (PSRFs), and identifies which PSRF has the strongest association with having a probable psychiatric disorder. Methods A cross-sectional study conducted in March 2018 involved a representative sample of the French working population. The General Health Questionnaire 28 (GHQ-28) was used to estimate the prevalence of probable psychiatric disorder and 44 items were gathered from theoretical models of PSRFs. We used multiple logistic regression to estimate the association of each PSRF with having a probable psychiatric disorder, adjusted on individual, health, and job confounders. Results This study involved 3200 French participants. The proportion of probable psychiatric disorder was 22.2% [20.6; 24.0]. Ten PSRFs were significantly associated with it. The strongest association was for having problems handling professional and personal responsibilities (reported by 15% of the study population) (OR = 1.97 [1.52; 2.54]), with 45% pathological GHQ-28 scores (potential psychiatric cases) for people exposed to this PSRF versus 18% non-exposed. The next strongest association was lack of support of colleagues (reported by 28%) (OR = 1.63 [1.29; 2.06]). The third strongest association was feeling sometimes afraid when doing the job (reported by 63%) (OR = 1.53, [1.21; 1.93]). Conclusions Our study identified 10 PSRFs associated with psychiatric disorder, with substantial exposure rate among the population. The results of our research could help develop recommendations to improve work environment.