Little is known about the health-related quality of life (HRQoL) and work-related stress and its risk factors among white-collar businessmen and management workers that migrate to high-income developing countries. A structural questionnaire survey was administered to 156 white-collar Taiwanese management personnel of representative companies of their industries in Taiwan, who were assigned long-term job positions in China. Questionnaire content included demographics and medical history, self-reported physical and mental conditions, personal lifestyle and behavior, Beck Depression Inventory, and information on HRQoL. White-collar migrant workers reported a high prevalence of alcohol consumption (72.4%) and perceived work-related stress (62.2%), and a lower prevalence of regular exercise (12.2%). Workers with higher levels of perceived work-related stress reported more alcohol consumption, a history of hyperlipidemia, and a higher prevalence of self-reported neck pain, poor sleep, and mild/moderate/severe depression. In our primary multivariate risk model to determine lifestyle and work-related stress variables and HRQoL, perceived work-related stress and a feeling of depression negatively impacted both the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the SF-36 health survey. Hyperlipidemia and self-reported neck pain were associated with significantly lower PCS scores, whereas cardiovascular disease, gastric ulcer, and poor sleep were associated with statistically lower MCS scores. White-collar migrant workers are generally younger with high socioeconomic status. Perceived work-related stress and a feeling of depression indirectly affect HRQoL. Hyperlipidemia, self-reported neck pain, cardiovascular disease, gastric ulcer, and poor sleep also had a significant negative impact on HRQoL.