Objective To examine the moderating effect of smartphone addiction on the relationship between social skills and anxiety among left-behind secondary school students. Methods A cross-sectional questionnaire survey was conducted among 1 522 students from six secondary schools in Jiangsu Province between November 2023 and April 2024. According to left-behind status, students were classified into a left-behind group (n=550, 36.14%) and a non-left-behind group (n=972, 63.86%). Social skills, anxiety, and smartphone addiction were assessed using the Chinese version of the Social Skills Improvement System Rating Scales (SSIS-RS-C), the Screen for Child Anxiety Related Emotional Disorders (SCARED), and the Smartphone Addiction Scale-Short Version (SAS-SV), respectively, and differences between the two groups were compared. Latent profile analysis was used to identify latent profiles of social skills among left-behind students. Hierarchical linear regression and the Johnson-Neyman method were used to examine the moderating effect of smartphone addiction on the relationship between social skills and anxiety. Results Compared with the non-left-behind group, the left-behind group had higher scores for smartphone addiction and anxiety and lower scores for social skills (P<0.05). The total SSIS-RS-C score negatively predicted the total SCARED score (β=-0.305, P<0.05), whereas the total SAS-SV score positively predicted the total SCARED score (β=0.189, P<0.05). The interaction between the total SSIS-RS-C score and the total SAS-SV score negatively predicted the total SCARED score (β=-0.138, P<0.05). Latent profile analysis identified three profiles of social skills among left-behind students: good, average, and deficient. In the average and deficient profiles, when the total SAS-SV score exceeded 24.37 and 31.27, respectively, the total SSIS-RS-C score was negatively associated with the total SCARED score (B=-0.027 and -0.030, respectively; both P<0.05), and this negative association strengthened as the total SAS-SV score increased. Conclusions Smartphone addiction moderates the relationship between social skills and anxiety among left-behind secondary school students; anxiety is more pronounced in those with poorer social skills and higher levels of smartphone addiction.