The authors examined the contributions of perceived family intrusiveness to career decision-making difficulties (CDMD) and the mediating effect of family orientation as a personality trait in different cultural settings. In Study 1, a web-based survey of 1,563 Hong Kong college students showed that perceived family intrusiveness significantly contributed to CDMD. This relationship was mediated by the relational personality trait emphasizing family orientation. Study 2 compared this pattern of relationship between a Hong Kong sample of 392 college students and a U.S. sample of 367 college students. The mediation model was only supported in the Hong Kong sample. Specifically, although the contributions of family intrusiveness to CDMD were demonstrated across the 2 cultural settings, the significant influences of family orientation were only supported in the Hong Kong sample. Implications for career development and counseling with college students from different cultural backgrounds are discussed.