Background <p>Sepsis-induced myocardial dysfunction (SIMD) is a frequent consequence in septic patients and is correlated with higher mortality. Recent research suggests that activating autophagy might alleviate SIMD. Thus, this study aims to identify the autophagy-related gene (ARG) and assess its diagnostic value in SIMD patients.</p> Methods <p>We conducted a sequential and extensive bioinformatics analysis of human SIMD transcriptome data from the Gene Expression Omnibus (GEO) database. Target ARG in SIMD were identified through weighted gene co-expression network analysis (WGCNA), differential expression analysis, and protein–protein interaction (PPI) network construction. The diagnostic value of the key ARG and its association with immune cell infiltration were evaluated. The role of target ARG in SIMD was validated using a lipopolysaccharide (LPS)-induced cell SMID model.</p> Results <p>We identified 12 ARGs associated with SIMD pathogenesis based on the human SIMD transcriptome data and investigated their potential biological processes. <i>MYC</i> was identified as a key ARG in SIMD by constructing a protein-protein interaction network. <i>MYC</i> was highly expressed in patients with SIMD and had excellent diagnostic capability for SIMD. Subsequently, we predicted drugs associated with <i>MYC</i> expression and constructed a crucial transcription factor (TF)-miRNA-mRNA co-regulatory network. Finally, we found that several immune-related signaling pathways were significantly activated in the <i>MYC</i>^high group, and <i>MYC</i> was correlated with the infiltration of immune cells in SIMD patients. In an LPS-induced SIMD cellular model, <i>Myc</i> knockdown attenuated the LPS-induced enhancement of autophagic flux.</p> Conclusion <p>We identified <i>MYC</i>, an autophagy-related gene, as a potential diagnostic marker for SIMD, offering insights into autophagic mechanisms and informing future diagnostic approaches.</p>