The purpose of the study was to identify the mediating effects of health promoting lifestyle in the relationship between life stress and adaptation to college life of health department college students. The data was collected for 10 days form sept. 3 to 14, 2012. Among a total of 351 cases of questionaries, only 342 cases were used. To data were analyzed by frequency, t-test, ANOVA, correlation and a hierarchical multiple regression analysis as suggested by Baron and Kenny(1986) using PASW statistics 18.0. From the analyses, there was a negative relationship between life stress and adaptation to college life but a positive relationship between health promoting lifestyle and adaptation to college life. There was a partial mediating effect of health promoting lifestyle between life stress and adaptation to college life. The results indicate a need to develop programs that effectively promote the health promoting lifestyle of health department college students to decrease life stress and maximize adaptation to college life.