AIMS: Autism spectrum disorder (ASD) is classified as a neurodevelopmental disorder. Individuals with ASD exhibit a higher incidence of tactile hypersensitivity. However, the underlying mechanisms remain unclear. The dorsal root ganglion (DRG) plays a crucial role in influencing tactile processing. This study aims to integrate RNA sequencing (RNA-seq) and molecular biology experiments to identify key molecules involved in tactile hypersensitivity in ASD, further investigate related mechanisms, and develop effective intervention strategy. MAIN METHODS: Using BTBR as the ASD model mouse and wild-type C57BL/6J as the control mouse, the differences in tactile sensitivity between them was compared. DRG were collected for RNA-seq analysis. Immunofluorescence and Enzyme-linked immunosorbent assay (ELISA) techniques were employed to validate the identified key molecules. And combined western blot to investigate the associated regulatory pathways. KEY FINDINGS: BTBR mice exhibit tactile hypersensitivity, which are associated with the upregulation of IGF-1 in the DRG. IGF-1 regulates the expression of Piezo2 ion channels. Inhibition of the IGF-1/Piezo2 pathway can significantly alleviate tactile hypersensitivity and social deficits in BTBR mice. Additionally, gentle touch intervention has been shown to reduce the overexpression of IGF-1/Piezo2 in the DRG, thereby ameliorating ASD symptoms. SIGNIFICANCE: The upregulation of the IGF-1/Piezo2 pathway in DRG may serve as a potential mechanism for tactile hypersensitivity observed in BTBR mice. Restoring the normalization of the IGF-1/Piezo2 is crucial for alleviating tactile hypersensitivity and synergistically rescues social deficits. Gentle touch intervention has the potential to ameliorate these behaviors through regulating IGF-1/Piezo2, positioning it as a promising strategy for ASD.