Autism spectrum disorder (ASD) is a neurodevelopmental disorder, which causes social deficits in social lives. Early ASD screening for children is an important method to reduce the impact of ASD on people’s whole lives. Traditional screening methods rely on protocol experiments and subjective evaluations from clinicians and domain experts and thereby cost a lot. To standardize the process of ASD screening, we 1 collaborate with a group of ASD experts, and design a ”Responsive Social Smile” protocol and an experiment environment. Also, we propose a machine learningbased assessment framework for early ASD screening. By integrating technologies of speech recognition and computer vision, the framework can quantitatively analyze the behaviors of children under well-designed protocols. By collecting 196 test samples from 41 children in the clinical treatments, our proposed method obtains 85.20% accuracy for the score prediction of individual protocol, and 80.49% unweighted accuracy for the final ASD prediction. This result indicates that our model reaches the average level of domain experts in ASD diagnosis.