In order to investigate the role of rheumatoid arthritis (RA)-related pathways in lung squamous cell carcinoma (LSCC). By obtaining gene expression data for RA and LSCC from the GEO and TCGA database, differentially expressed genes were screened using GEO2R tool and Rstudio software. GO/KEGG functional enrichment analysis identified key genes in the RA signaling pathway. Combining SNP data from the IEUopenGWAS database, Mendelian randomization analysis was used to assess the causal relationship between the RA signaling pathway and LSCC. The constructed gene-drug and ceRNA networks, along with immune cell infiltration analysis, revealed 188 co-expressed differential genes, mainly enriched in the RA signaling pathway. Mendelian randomization analysis showed that increased activity of the RA signaling pathway is associated with a reduced risk of LSCC. This study provides new insights into the pathogenesis and potential research directions for the treatment of LSCC.