This study explored the relationship between social interaction anxiety (SIA) and problematic smartphone use (PSU) among Chinese adolescents. Further, the roles of online basic psychological needs satisfaction (online BPNS), nature connectedness (NC), and related differences between urban and rural adolescents were examined. We recruited 840 Chinese adolescents to complete a questionnaire. Results showed that online BPNS mediated the relationship between SIA and PSU after controlling for sex, age, duration of smartphone use, and rural-urban differences. NC moderated the mediating effect of online BPNS as a second-stage moderator, and the mediating effect was stronger for adolescents with lower NC. The indirect effect of SIA on PSU through online BPNS depended on NC. Our findings suggested that reducing SIA and online BPNS levels, enhancing connection with nature, and training adolescents (especially rural adolescents) on methods to seek social support and develop social abilities can effectively deal with PSU.