Aim GEO database was used to explore the common pathogenesis of gout complicated with atherosclerosis (As). Methods The gene expression matrices of gout (GSE160170) and As (GSE100927) were downloaded from the GEO database, the differentially expressed genes (DEG) of gout and As were analyzed, and enrichment analysis was performed separately. After analyzing the common differentially expressed genes (CDEG), functional enrichment analysis, protein-protein interaction (PPI) network analysis, and hub genes (HG) identification were performed on them, and co-expression analysis and validation were performed on hub genes. Finally, the immune cell infiltration of gout and As was analyzed, and the correlation between hub genes and infiltrating immune cells (IIC) was explored. Results The GSE160170 dataset obtained 1 606 differentially expressed genes, while the GSE100927 dataset obtained 481 differentially expressed genes. The enrichment analysis of 22 differentially expressed genes showed that the regulation of cytokines may be the key mechanism of gout complicated with As. Six hub genes (CCR2, CD2, FCGR3A, FGD3, IL10RA, SIGLEC1) were identified using the CytoHubba plugin, and the validation results of these hub genes showed that they were still reliable. The co-expression network showed that these hub genes could affect the regulation of tumor necrosis factor superfamily cytokines. Immune cell infiltration analysis showed that the expression of NK cells in gout was significantly increased, and was significantly related to CCR2 gene. The expression of living fertilizer large cells in As was significantly increased, and was significantly related to CD2 gene. Conclusion The regulatory effect of tumor necrosis factor superfamily cytokines may be the core factor of gout complicated with As.