The present study investigated whether the interaction of resting RSA (respiratory sinus arrhythmia) and RSA reactivity was associated with mobile phone addiction in adolescents. Physiological and psychological data were collected from 165 Chinese adolescents (80 boys; Mage = 12.68, Sage = 0.69). The results revealed that (1) resting RSA and RSA reactivity were both significantly negatively correlated with adolescents’ mobile phone addiction; and (2) resting RSA and RSA reactivity interactively to predict adolescents’ mobile phone addiction. Specifically, adolescents with higher resting RSA and higher RSA reactivity showed the lowest level of mobile phone addiction. The findings suggest the importance of considering the combined indices of respiratory sinus arrhythmia in predicting adolescent problem behaviors.