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Lysozyme (LYZ) is a naturally occurring antimicrobial protein first discovered in the 1920s. As a key component of innate immunity, its antimicrobial effects and immunomodulatory functions in bacterial defence have been extensively characterized. However, emerging evidence since the 1950s has revealed its complex involvement in tumour progression, with conflicting reports of both tumour-suppressive and tumour-promoting effects across different cancer types. A critical knowledge gap remains in understanding the mechanistic basis for this duality, exacerbated by reliance on single-omics approaches and small cohorts in previous studies. This review focuses on mammalian C-type LYZ (referred to as LYZ hereafter unless specified) and integrates multi-omics data (transcriptomics and proteomics) with clinical and mechanistic research to systematically dissect its dual roles in cancer. By analysing cross-cancer heterogeneity through multi-omics perspectives, we emphasize its dual promise as both a prognostic biomarker and an actionable therapeutic target, aiming to provide new insights for precision oncology. KEY POINTS: LYZ is a multi-functional secreted factor that encompasses both antibacterial and immunomodulatory functions. Emerging evidence highlights its complex role in tumour progression by directly influencing tumour cells and modulating the immune microenvironment. LYZ is a promising potential biomarker and therapeutic target in some cancers.