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Staphylococcus epidermidis has been many virulence agents which instantly prompt damage to its host tissues. The capability to forming a biofilm is considered one of the most major virulence agents for many types of bacteria included S. epidermidis to supporting any illness. A biofilm is usually formed by attached microbial cells sessile within a matrix of extracellular polymeric substances (EPS). EPS has been consisted of; proteins arranged from one to two percentage including enzymes, RNA, and DNA less than one percent, while the polysaccharides were one to two and the main remaining composition is, water up to 97% that is liable to the movement of nutrients inside the biofilm components. Current knowledge leads to small RNAs (sRNAs) bis- (3'-5')-cyclic di-guanosine monophosphate (c-di-GMP) and quorum sensing (QS) as the primary arranger of bacterial biofilms formation. QS-controlled genes constituted about 10% of the total bacterial genome. Biofilm composition is reliant on the stimulation of certain genes expression that leads to the starting point of biofilm foundation. So, the present study aimed to study the impact of Al2O3 & Fe3O4 nanoparticles on extracellular matrix-binding protein (embp), autolysin E (atlE), and Tntercellular adhesion protein C (icaC) genes expression level which are involved in biofilm-forming of S. epidermidis bacteria. By using real-time quantitative polymerase chain reaction (RT-qPCR) assay. The result showed significantly impact (P < 0.05) of Al2O3 & Fe3O4 nanoparticles on expression levels of (embp), (atlE), and (icaC) genes. [ABSTRACT FROM AUTHOR]