The emergence of antibiotic-resistant bacteria has been of great concern due to the difficulty in chemotherapy. The aim of this study was to evaluate the resistance phenotypes and gene expression in wild-type and antibiotic-induced resistant Staphylococcus aureus exposed to oxacillin and ciprofloxacin. The wild-type S. aureus was highly resistant to oxacillin after the exposure to oxacillin, while the oxacillin resistance was not changed when exposed to ciprofloxacin. The resistance of oxacillin- and ciprofloxacin-induced S. aureus to penicillin was resulted from the production of β-lactamase, corresponding to the overexpression of blaZ (>2-fold). The efflux pump-related genes (norA, norB, norC, mdeA, mepR, mgrA, and lmrS) were overexpressed in oxacillin- and ciprofloxacin-induced S. aureus, leading to the increase in the resistance to aminoglycosides and quinolones. It is worth noting the relationship between resistance phenotype and resistance genotype in terms of antibiotic susceptibility and differential gene expression.