<p>The predictive effect of stressful life events on problem gambling has been a hot topic in the field of addiction research. However, few studies have explored the underlying mechanisms. This study verifies the complete prediction process from stressful life events to problem gambling in the form of a quantitative study based on the structural equation modeling of gambling in Mainland China. Specifically, this study aims to explore the serial mediating effect of difficulties in emotion regulation and coping motives in the relationship between stressful life events and problem gambling. The participants in this study were 455 lottery gamblers from a province in Mainland China (Mage = 35.356, SD = 9.678, 32.967% female). They completed four assessments: the Problem Gambling Severity Index, the Holmes-Rahe Stress Inventory, the Brief Version of the Difficulties in Emotion Regulation Scale, and the coping motives dimension of the Gambling Motives Questionnaire. The results showed that stressful life events had a significant positive predictive effect on problem gambling. Additionally, difficulties in emotion regulation positively predicted coping motives and mediated the relationship between stressful life events and problem gambling. Furthermore, difficulties in emotion regulation and coping motives played a serial mediating role in this relationship. However, coping motives alone did not significantly mediate the relationship between stressful life events and problem gambling. The contribution of this study is to elucidate the complete process by which stressful life events predict problem gambling, providing new insights and intervention strategies for the prevention of problem gambling in problem gamblers, including relieving stress through mindfulness, improving emotion regulation, and establishing correct gambling motivation. At the same time, it also fills the gap in the international gambling research that Chinese mainland samples are scarce.</p>