Background and Objectives: Studies have verified that family functioning has a negative relationship with smartphone addiction in adolescents. However, not much is known about the mediating mechanism underlying this relationship during the Coronaviruses Outbreak. Hence, the aim of the present study was to investigate the mediating role of self-esteem and loneliness in the relationship between family functioning and smartphone addiction. Materials and Methods: The research design was descriptive. From the statistical population of male high school students at district 14 of Tehran in academic year of 2019-2020, a total of 281 students were selected using convenience sampling method. Data were collected using Family Assessment Device, UCLA Loneliness Scale-Version 3, Cell-phone Over-use Scale, and Rosenberg Self-Esteem Scale. To analyze the data Pearson’, s correlation test and structural equation modeling were conducted. Results: The results showed that direct effect of family functioning (β, =0. 11, p<0. 001), self-esteem (β, =0. 27, p<0. 001), and loneliness (β, =0. 23, p<0. 001) on the smartphone addiction were significant. Also, the results showed that the mediating role of self-esteem (β, =-0. 11, p<0. 01) and loneliness (β, = 0. 04, p<0. 05) in the relationship between family functioning and smartphone addiction was significant. Conclusion: This study revealed that the adolescents who live in better family atmosphere have higher self-esteem and experience less loneliness, and are less likely to develop smartphone addiction. Overall, these findings have some important implications for the prevention and intervention of the adolescent Internet addiction.