Adolescence is a developmental phase in which feelings of loneliness often increase. It is also a time period during which computer-mediated communication (CMC) is frequently used by youth to communicate with their peers. Strong family relationships protect youth from experiencing a wide range of adversities and mental health problems, including loneliness, and yet use of CMC to contact peers may leave adolescents feeling disconnected and lonely while also limiting the amount of time they spend with their family. This study examines the association between CMC and feelings of loneliness among Canadian youth, with family communication explored as an effect modifier. The study base was the Canadian 2013-2014 Health Behaviour in School-aged Children study used in a cross-sectional analysis (N = 30117; grades 6-10). Random-effects multilevel Poisson regression methods were used to quantify risks for adolescent loneliness among daily vs. non-daily users of verbal CMC (e.g., Skype, phone calls), text/instant messaging and social media CMC with friends. Effect modification was tested via the inclusion of modelled interaction terms. Family communication quality moderated the relationship between daily CMC use and loneliness among Canadian youth. Among youth experiencing high relative quality of family communication, daily use of verbal and social media CMC to contact friends was positively associated with reports of loneliness, compared to non-daily users. Findings suggest that family communication must remain central in societal discussions of youth loneliness, mental health and use of CMC.