Abstract: Objective To analyze the gene expression patterns in human intervertebral disc, so as to screen out the key signaling pathways and core genes that may be involved in intervertebral disc degeneration (IDD). Methods After downloading two sets of mRNA expression data sets (GSE223130 and GSE15227) from GEO database, we screened the differential expressed genes (DEGs) in the intervertebral disc tissues with Thompson grading of high level and low level respectively. After the intersection of the two, we got the final real DEGs, and analyze the gene ontology (go) and gene enrichment of Kyoto Encyclopedia of genes and genomes (KEGG). Protein-protein interaction (PPI) network was constructed, and the core modules of PPI network were screened and KEGG enrichment analysis was carried out to find out the key signal pathways of core genes related to IDD. Results We found that PI3K-Akt signal pathway, focal adhesion and human cytomegalovirus infection could be the key signal pathways involved in IDD. In addition, we identified 10 core genes GAPDH, TP53, FN1, ACTB, EEF1A1, CCT2, COL1A1, ACTG1, PPP2CA and RPLP0, involved in IDD, which may be candidate genes for future IDD therapy. Conclusions This study identified for the first time the key signaling pathways that may be related to IDD: PI3K-Akt signaling pathway, Focal adhesion and human cytomegalovirus infection, etc., and screened 10 candidate core genes, which provided new targets and approaches for gene therapy of IDD.