Background: Small-cell lung cancer (SCLC) remains the leading form of malignant lung cancer, but little bioinformation on SCLC is available. This study explored the molecular targets of SCLC by evaluating differentially expressed genes (DEGs) and differentially expressed microRNAs (miRNAs) (DEMs).Methods: Five mRNA expression profiles and two miRNAs expression profiles from Gene Expression Omnibus (GEO) were downloaded. R software was utilized to analyze the DEGs and DEMs between SCLC and normal samples. The DEGs were analyzed via functional enrichment analyses and were used to construct protein-protein interaction (PPI) networks. DEM targets were then predicted and intersected with the DEGs. Furthermore, the hub genes of SCLC in the overlapping DEGs were analyzed in Oncomine. Finally, the expression of DEM-hub gene pairs were verified in tissues by RT-qPCR and Western blotting.Results: In total, 236 common DEGs and 104 common DEMs were identified. Functional enrichment analysis showed the DEGs were primarily enriched in ‘cell cycle’, ‘DNA replication’ and ‘oocyte meiosis’. Twenty hub genes and five modules were identified from the PPI network. Furthermore, 6732 targeted genes of the DEMs were predicted. After intersecting with DEGs, 54 genes and 153 miRNA-mRNA pairs were eventually identified aberrant regulation in SCLC. MiR-445-3p/TTK, miR-140-5p/TTK and miR-133b/CDCA8 were identified as DEM-hub gene pairs. Oncomine analysis confirmed the overexpression of TTK and CDCA8 in SCLC. Further validation demonstrated that TTK and CDCA8 levels in SCLC tissue samples were markedly increased relative to normal controls, while miR-445-3p, miR-140-5p, and miR-133b levels were lower in SCLC samples than in controls.Conclusions: Our results revealed key miRNA-mRNA pairs associated with SCLC, providing new insights into potential disease targets.