A disintegrin and metalloproteinase (ADAM) 28 belongs to the zinc-dependent metalloproteinase superfamily and has a signal sequence at its N-terminus that can direct the protein into the secretory pathway. ADAM28 is a multifunctional protein that has been shown to play a role in regulating numerous biological processes, including cell adhesion, cell fusion, membrane protein shedding, protein hydrolysis, and signaling pathway modulation. ADAM28 is highly expressed in numerous malignant tumors and plays a pivotal role in the proliferation, metastasis and drug resistance of these tumors by acting on substrates such as IGFBP-3, vWF and CTGF, thereby promoting PSGL-1/P-selectin-mediated cell adhesion. Consequently, inhibiting ADAM28 could impede tumor proliferation, metastasis and drug resistance, which suggests that ADAM28 may serve as a prognostic indicator of and potential therapeutic target for malignant tumors. In this article, the structure and function of ADAM28 and its correlation with the onset and progression of human malignant tumors are primarily examined. Additionally, the potential applications of ADAM28 in tumor research are investigated to offer a theoretical foundation and reference for the clinical diagnosis and treatment of malignant tumors.