To use bioinformatics to analyze the gene chip data of the tissue surrounding the hematoma and control samples from patients with intracerebral hemorrhage (ICH), identify key molecules related to cell pyroptosis after ICH, and further explore the pathological mechanisms and potential therapeutic targets of ICH. Methods: Differentially expressed gene profiles were selected from the GEO database for the tissue surrounding the hematoma of four ICH patients and the corresponding normal brain tissue samples (white and gray matter) from the contralateral side. The differentially expressed genes (DEGs) and pyroptosis-related genes (PRGs) were merged and analyzed to identify differentially expressed PRGs (DE-PRGs). GO, KEGG enrichment analyses, and protein-protein interaction (PPI) analyses were performed on the identified DE-PRGs. Results: Compared with control tissue, a total of 44 DE-PRGs were found in the tissue surrounding the hematoma. GO and KEGG analyses indicated that these 44 DE-PRGs were mainly enriched in processes such as apoptosis, positive regulation of inflammatory response, positive regulation of the NF-κB pathway, NOD-like receptor signaling pathway, and pyroptosis. PPI analysis of the 44 DE-PRGs identified 10 key genes: IL-1 β, CXCL8, STAT3, TLR2, CASP1, ICAM1, IRF1, PTGS2, NLRP3, and IL1RN. GO enrichment functional analysis showed that these key genes were significantly enriched in inflammatory response, pyroptosis, and signaling pathways. Conclusion: This study identified 44 DE-PRGs related to pyroptosis after ICH through bioinformatics analysis and further screened out 10 key genes through PPI analysis. Functional analysis showed that all were related to the mechanism of pyroptosis after ICH and may be potential therapeutic targets for ICH.