Objective To screen microRNA (miRNA) with elevated expression in intervertebral disc degeneration (IDD) tissues, and to explore its role and possible mechanisms in IDD. Methods Two published IDD miRNA sequencing databases were compared to screen the most highly expressed miRNA-miRNA-603. Intervertebral disc tissues of 10 patients with IDD and 10 patients with lumbar spine fracture were collected, and the nucleus pulposus cells from normal intervertebral disc tissues were isolated and cultured. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miRNA-603 in the IDD and normal intervertebral disc tissues. The role of miRNA-603 in tumor necrosis factor α (TNF-α)-induced inflammation of nucleus pulposus cells was explored using miRNA-603 mimics and inhibitor factor. Sorbin and SH3 domain-containing protein 3 (SORBS3), a target gene of miRNA-603, was found by using bioinformatics website and the published IDD miRNA sequencing databases, and was verified by dual-luciferase reporter assay. The function of miRNA-603 and SORBS3 in the inflammatory response of nucleus pulposus cells was explored by the overexpression of miRNA-603 and SORBS3. Results The expression of miRNA-603 increased significantly in IDD tissues (P<0.01). Overexpression of miRNA-603 could promote the expression of interleukin (IL)-6 and IL-1β in nucleus pulposus cells (both P<0.01); inhibition of the miRNA-603 expression could reduce the TNF-α-induced expression of IL-6 and IL-1β (P<0.01, P<0.05). At the same time, the expression of cleaved caspase-1 also decreased (P<0.01). Bioinformatics prediction showed that miRNA-603 could targetedly regulate SORBS3, and the expression of SORBS3 in IDD tissues was low (P<0.01). Compared with the overexpression of miRNA-603 alone, co-overexpression of miRNA-603 and SORBS3 inhibited the TNF-α-induced expression of IL-6 and IL-1β in nucleus pulposus cells (both P<0.01). Conclusion The expression of miRNA-603 increases in human IDD tissues. miRNA-603 can induce the inflammatory response of nucleus pulposus cells by targetedly inhibiting SORBS3, which may promote the IDD process.