Lung cancer (LC), particularly lung adenocarcinoma, is a leading cause of cancer-related mortality, while systemic sclerosis–associated interstitial lung disease (SSc-ILD) is a chronic fibrotic autoimmune disorder. Growing evidence suggests shared molecular mechanisms between these conditions, although their genetic overlap remains insufficiently characterized. In this study, integrative bioinformatics approaches were applied to identify common differentially expressed genes (DEGs) and regulatory networks linking LC and SSc-ILD. Comparative transcriptomic analysis revealed 72 shared DEGs, including 10 hub genes: MMP7, CXCL14, and CD79A (upregulated), and CXCR2, IL1A, FCAR, GRIA1, IL1R2, CSF3, and FFAR2 (downregulated). Regulatory network analysis identified key miRNAs (hsa-miR-34a-5p, hsa-miR-126-3p, hsa-miR-335-5p) and central transcription factors (FOS, JUN, NFKB1). Pathway enrichment highlighted interleukin-10 signaling as a critical shared pathway, implicating immune regulation and extracellular matrix remodeling. Molecular docking suggested a potential interaction between doxycycline and MMP7 (binding affinity −6.4 kcal/mol), while X-ray diffraction and Rietveld refinement confirmed its crystalline purity. Additionally, doxycycline demonstrated antibacterial activity against Staphylococcus aureus via minimum inhibitory concentration assays. Overall, these findings provide preliminary insights into shared molecular features between LC and SSc-ILD and suggest doxycycline as a potential repurposed candidate warranting further experimental and clinical validation.