In recent years, there has been a high concern on childhood disorders among experts and parents. A large number of therapeutic interventions were based on the direct interaction with the child therapist. The purpose of this study was to investigate the efficacy of parent-child interaction therapy (PCIT) in reducing depression, anxiety and stress in children. This randomized clinical trial was conducted at Bijan Substance Abuse Treatment Center in Tehran, Iran, from December 15, 2013, to November 20, 2014. Fifty children (N=50, aged between 4 and 6 years, and M = 5.2 ± .38) who achieved scores above the cut-off point based on DASS-21 questionnaire, were selected and randomly divided into two experimental (n=25) and control (n=25) groups. Parent-child interaction therapy was performed in terms of the independent variable for ten 45-minute sessions. The data was analyzed using chi-square and MANCOVA model. Also, the qualitative data, which resulted from the demographic evaluations, was coded and analyzed by instrument of analyzing qualitative data, Atlas.ti, Version 5.2. The results showed that CPRT had significantly reduced depression, anxiety and stress in children (p