More and more excellent minority college students pursue advanced studies in Han district colleges. To pursuit well-being is the ultimate goal of the common pursuit of human activity(Chen & Li, 2014; Liu, Tian, Huebner, Zheng, & Li, 2014; Wang, Huang, & Bi, 2014). Previous researchers found that well-being among minority college students in Han district colleges was lower than well-being among common college students (Chen, 2012; Yang & Ye, 2014; Ye &Yang, 2014). It is very necessary to study factors and the potential mechanisms that influence well-being among minority college students in Han district colleges in order to improve well-being among minority college students in Han district colleges. The present study aimed to explore the moderated mediation among sense of cultural alienation, coping style, cultural intelligence and well-being among minority college students in Han district colleges. A sample of 670 minority college students in Han district colleges of 6 college (342boys and 328 girls, Mage=20.16±.86) was recruited in the study to complete self-report questionnaires. The self-report questionnaires used in this study included sense of cultural alienation questionnaire, coping style scale, cultural intelligence questionnaire and well-being questionnaire． The results indicated that: (1) coping style mediated the effect of sense of cultural alienation on well-being among minority college students in Han district colleges. Cultural alienation not only directly influence well-being among minority college students in Han district colleges, but also through influence coping style, ultimately influence well-being among minority college students in Han district colleges. (2) cultural intelligence moderated this mediation effect of coping style. Cultural intelligence not only moderated the relationship between cultural alienation and coping style, but also moderated the relationship between cultural alienation and well-being among minority college students in Han district colleges. For minority college students in Han district colleges with high levels of cultural intelligence, with the increase of sense of cultural alienation, minority college students’ positive coping style, negative coping style and well-being had no obviously ascending trend (β= –.07, t = –1.35, p >.05; β= –.02, t = –.37, p > .05; β= –.04, t = –.51, p > .05)．For minority college students in Han district colleges with low levels of cultural intelligence, with the increase of sense of cultural alienation, minority college students’ positive coping style and well-being had obviously descending trend (β= –.29, t = –5.24, p < .001；β= –.46, t =–5.72, p < .001), and minority college students’ negative coping style had ascending trend (β= .18, t = –3.19, p < .01). To sum up, the effect of sense of cultural alienation on well-being among minority college students in Han district colleges was moderating mediating effect. The moderating mediating model deeply revealed the effect mechanism of the effect of sense of cultural alienation on well-being among minority college students in Han district colleges. These findings supported our model that the link between sense of cultural alienation and well-being among minority college students in Han district colleges was complex and dependent on other factors. The theoretical and practical implications of the results was further discussed.