Social media are increasingly adopted in university administration, teaching, and learning. For pre-service teachers, although there is growing evidence suggesting the effectiveness of educational technology courses in enhancing their technological pedagogical content knowledge (TPACK), relatively little is known about whether and how this knowledge is associated with social media usage (SMU) in informal settings. In this study, the relationships between SMU in informal settings and TPACK among pre-service teachers were investigated. Based on the survey data of a sample of 212 pre-service teachers in Hong Kong, media sharing was found to be a significant positive predictor of technology knowledge and knowledge of teaching with technology, whereas Internet searching and video gaming were not predictive of any component of TPACK. The findings of the study were interpreted in the light of the educational affordances of social media technologies, and their implications for researchers and teacher educators were discussed.