Aims. Accumulating evidence reported that the microRNA (miRNA) took an important role in intervertebral disc degeneration (IDD). In this study, we revealed a novel miRNA regulatory mechanism in IDD. Main Methods. The miRNA microarray analyses of human degenerated and normal disc samples were employed to screen out the target miRNA. In vitro and in vivo experiments were conducted to verify the regulatory effect of miR‐101‐3p. Key Findings. The expression level of miR‐101‐3p was significantly decreased in the degenerated disc samples which were confirmed by qRT‐PCR. Moreover, the miR‐101‐3p expression level was changed dynamically according to the disc degeneration grade. Upregulation of miR‐101‐3p expression level inhibited cell apoptosis. Furthermore, stanniocalcin‐1 (STC1) was selected to be the target gene of miR‐101‐3p according to the bioinformatic algorithms. Mechanically, upregulation of miR‐101‐3p significantly decreased the expression of STC1, vascular endothelial growth factor (VEGF), and MAPK pathway expression levels. Therapeutically, in vivo experiment on IDD rat model illustrated that agomir‐101‐3p could effectively suspend IDD. Significance. Our findings demonstrated that miR‐101‐3p alleviated IDD process through the STC1/VEGF/MAPK pathway.