Objective To explore the application of iPad-based software Let'S Talk in the rehabilitation of children with autism. Methods From March to September, 2015, iPad-based software Let'S Talk was applied in four children with autism. The language ability, emotion and behavior control ability, self-consciousness and eye contact were observed. The Psycho-educational Profile-3rd (PEP-3), Autism Behavior Checklist (ABC) and Childhood Autism Rating Scale (CARS) were used to access the months of age, behavior characteristics, and the severity of autism before and after application. Results The language ability and behavior control ability improved, as well as the self-consciousness and eye contact, and the bad behaviors reduced. The months of age rose in PEP-3, and the scores of ABC and CARS decreased. Conclusion IPad-based software Let'S Talk could be applied in the rehabilitation of children with autism.