Objective: To explore mental health among minority students in Han middle schools and to analyze the difference of mental health between junior and senior high school students, with the aim of providing a reference for the relationship between cultural alienation and mental health of minority students in Han middle schools. Methods: Participants were 1 679 minority students in two Han middle schools recruited from Datong county in Qinghai province, participants completed cultural alienation and mental health inventroy of middle school students. Results: Prevalence of mental health problems illustrated a‘V’ shape curve for both junior and senior high school minority students in Han middle schools. Junior school students scored lower than senior high school students on obsessive, learning anxiety, learning pressure, maladjustment and emotional imbalance(t=-2.88, -5.17, -2.82, -1.99, -2.60, P<0.05). The detection rate of moderate and mild mental health problems (44.5%, 12.5%) between middle school students of Han nationality and minority nationality (50.3%, 6.9%)(χ2=13.22，P<0.01). The middle school students of minority nationality showed more hostile, interpersonal tension and sensitivity, depressed, maladjustment, psychological imbalance, and lesser obsessive(t=2.86, 1.97, 2.04, 5.11, 5.75, -13.17, P<0.05). After controlling for grade, gender and nationality, cultural isolation(β=0.22, t=5.12), cultural separateness(β=0.19, t=4.54) and discordant sense(β=0.08, t=2.39) was positively associated with mental health，the sense of control(β=-0.09, t=-2.02) was negative associated with mental health(P<0.05). Conclusion Mental health of middle school students of ethnic minorities in Han area is at a satisfactory level, The junior school students in Han middle schools had higher level of mental health, Cultural alienation is an important factor in keeping mental health.