Little is known about the job strain of staff working in disability institutions. This study investigated the staff's job strain profile and its determinants which included the worker characteristics and the psychosocial working environments in Taiwan. A cross-sectional study survey was carried out among 1243 workers by means of a self-answered questionnaire. The outcome variable (high-strain job) was evaluated. The explanatory variables were: worker characteristics and the psychosocial working environment evaluated according to Karasek's Job Demand-Control-Support model. The results show that many staff characteristics were correlated with job strain, such as staff's working hours, age, gender, job title, educational level, religion, in-job training, working years in disability institutions and Effort-Reward Imbalance factors. Organization factors, such as geographical, institutional ownership and accreditation performance and size were also correlated with staff's job strain. In multiple a logistic regression model of the job strain, we found that the factors of financial reward (high compare to low, OR = 0.95, 95% CI = 0.928-0.975), extrinsic effort (high compare to low, OR = 1.072, 95% CI = 1.072-1.158), perceived job stress (sometimes stressful compare to no stress, OR = 2.305, 95% CI = 1.161-4.575; very stressful compare to no stress, OR = 3.931, 95% CI = 1.738-8.893) of the staff were significantly correlated to the high job strain of the staff. An important focus of future research should be extending the findings to consider the factors to affect the high job strain to improve the well-being for staff working for people with intellectual disability. (Contains 9 tables.)