The cognitive evaluation of the process of interpersonal communication may be a risk factor of depression. Interpersonal communication competence assesses how people display performance on communication and has been proposed to impact directly need satisfaction, indirectly anxiety, stress, and depression. The main purpose of the present cross-sectional study was to examine the mediation roles of need satisfaction, anxiety, and stress in the association between interpersonal communication competence and depression. Correlational and mediation analysis were performed to test conceptual model of depression. Correlational analysis revealed that depression was associated with interpersonal communication competence, anxiety, and stress. Additionally, interpersonal communication competence was associated with need satisfaction, anxiety, and stress. As for mediation analysis, it was concluded that the serial mediation role of need satisfaction, anxiety, and stress in the association between interpersonal communication competence and depression was significant. A new conceptual model provided empirical evidences as to the prodrome of depression. Therefore, it was supposed that these findings would be effective in psychological interventions of depression.