Migratory figures place Chile as one of the South American countries with the most significant number of migrants. The present study evaluated the psychosocial occupational risks of migrant workers in the Maule Region and their association with health-related quality of life. Cross-sectional study with migrant workers between 18 and 60 years old, residing in the Maule Region (n = 145). The questionnaires applied were: a) SUSESO ISTA-21 Psychosocial Risk Questionnaire; b) SF-12 health and quality of life questionnaire; c) Socio-demographic questionnaire. We perform a bivariate statistical analysis with non-parametric tests of Mann Withney U, Kruskal Wallis, and Spearman correlation. The migrants with lower quality of life in terms of the physical health dimension are those who are divorced, widowed or single, who work less than 22 hours per week and arrived directly to the Maule Region from their countries of origin. The psychosocial risks related to double presence at work seem to be the dimension with the highest prevalence. Migrants who work between 33 and 43 hours per week a negative association between the number of hours worked and work rewards; lack of control, which strongly impacts job satisfaction due to insecurity; and exhaustion from overwork. Exposure to a new social and work environment could lead to different psychological responses in which anxiety, confusion, and culture shock affect the mental health of migrants. Coming into contact with a new culture is a complex process; it requires support networks, adaptation, and migration policies based on human rights.