The aim of the study is to examine the differences in the diversity of family factors between adolescents with and without Internet addiction and substance use experience. A total of 3662 students (2328 boys and 1334 girls) were recruited from seven junior high schools, six senior high schools, and four vocational high schools in southern Taiwan. Internet addiction and substance experience were classified according to the score of Chen Internet Addiction Scale Questionnaires for Experience of Substance use. The family factors assessed included perceived family satisfaction, family economic status, parents' marriage status, care-givers, the frequency of intra-family conflict, families' habitual alcohol use, and perceived parents' or care givers' attitude toward adolescents' substance use. This study demonstrated that the characteristics of higher parent-adolescent conflict, habitual alcohol use of siblings, perceived parents' positive attitude to adolescent substance use, and lower family function could be used develop a predictive model for Internet addiction in the multiple logistic regression analysis. The former three family factors were also sufficient in themselves to develop a predictive model for substance use experience. The results revealed that adolescent Internet addiction and substance use experience shared similar family factors, which indicate that Internet addiction and substance use should be considered in the group of behavioral problem syndromes. A family-based preventive approach for Internet addiction and substance use should be introduced for adolescents with negative family factors.