Many clinical studies have indicated an association between biomechanical factors and the incidence and pathological progression of adolescent idiopathic scoliosis (AIS). However, at present, the research on AIS is mainly focused on the etiology, and there are few studies reporting the causes of progressive aggravation of AIS. In the present study, we aim to investigate the role of Piezo1 in compressive stress-induced mouse spinal vertebral growth plate chondrocytes apoptosis. First, a scoliosis mouse model was established, and the expression of Piezo1 as well as the degree of apoptosis were investigated. We found that the expression of Piezo1 and the degree of apoptosis were significantly higher on the concave sides than that on the convex sides of the vertebral growth plate in mice with scoliosis. Spinal vertebral growth plate chondrocytes were further isolated and treated with Yoda1 to mimic Piezo1 overload. Excess Piezo1 significantly promoted apoptosis of spinal vertebral growth plate chondrocytes. Moreover, static gas compressive stress was used to simulate the increased concave compressive stress in the process of scoliosis with or without GsMTx4, a Piezo inhibitor. It was observed that with the increase of static compressive stress, the expression of Piezo1 increased, and the chondrocytes of vertebral growth plate treated with Piezo1 inhibitor GsMTx4 weakened the above phenomena. In conclusion, our results indicated that compressive stress is strongly associated with the different degrees of apoptosis on both sides on the convex and concave sides of the vertebral growth plate in scoliosis via inducing different expressions of Piezo1. Reducing the expression of Piezo1 in the concave side of the vertebral growth plate and inhibiting the apoptosis of chondrocytes in the bilateral vertebral growth plate caused by asymmetric stress on both sides of the concave vertebral body may be a promising treatment strategy for AIS.