Introduction: Currently, several approaches have been presented for treatment of children with Autism Spectrum Disorder (ASD). The aim of the present study was to compare the effectiveness of Holistic Multidimensional Treatment Model (HMTM) with Applied Behavioral Analysis (ABA) in the improvement of clinical symptoms of children with autism spectrum disorder.  Method: The present study had a Quasi experimental design. The sample included 20 children who were assigned with convenience sampling and randomly divided to 2 groups of ABA (8 boys and 2 girls) and HMTM (7 boys and 3 girls).The diagnosis was made by a child psychiatrist based on DSM-IV-TR criteria and using Autism Diagnostic Interview-Revised (ADIR) and Autism Diagnostic Observation Schedule (ADOS). Then the children were referred to Noore Hedayat center for the treatment. Childhood Autism Rating Scale (CARS), Bender Gestalt Test, Draw-A-Man Test Goodenough, Raven's Coloured Progressive Matrices Test for children ,Vineland Social Maturity Scale (VSMS) and performance charts of children based on their videotaped behaviors were used. Data analysis was done using ANCOVA test. Results: Findings showed that in spite of more effectiveness of HMTM compared to ABA, the differences of standard tests except Bender Gestalt Test and performance charts were not significant (P>0.05). Conclusion: In conclusion, HMTM at least had the equal effectiveness to ABA in the treatment of children with Autism Spectrum Disorder. Further researches are needed to compare the effectiveness of these 2 methods without limitations which occurred in this research.