Objective To evalue the ability of detecting the resistance of cefoxitin-sensitive,penicillin-resistant Staphylococcus by different methods and analyze the antibiotic susceptibility spectrum of coagulase-negative Staphylococcus which are non-mecA-mediated oxacillin resistance. Methods All the isolates were collected from Huashan hospital between 2007 and 2009. The isolates were recovered from various clinical sources, including respiratory tract, urine, secretion and sterile fluids samples. The oxacillin susceptibility of Staphylococcus aureus was determined by cefoxitin disk diffusion test, cefoxitin MIC test,oxacillin disk diffusion test and oxacillin MIC test Likewise, the oxacillin susceptibility of coagulasenegative Staphylococcus was determined by cefoxitin disk diffusion test and oxacillin MIC test. All the isolates with sensitive to cefoxitin were screened for the mec A gene by PCR Finally, the MIC of non-mecA-mediated oxacillin-resistant Staphylococcus were determined. Results Among 255 cefoxitin disk diffusion test sensitive and penicillin-resistant Staphylococcus aureus, 6 isolates were intermediated to oxacillin and 4 were resistant by oxacillin disk diffusion test, but all the isolates were sensitive by the cefoxitin disk diffusion test,cefoxitin MIC test and oxacillin MIC test. Among 75 cefoxitin disk diffusion test sensitive and penicillin-resistant coagulase-negative Staphylococcus, 16 isolates were resistant to oxacillin by oxacillin MIC method and 4 carried mecA gene. Among 12 non-mecA-mediated oxacillin-resistant Staphylococcus, the susceptible isolates of gentamicin is 10, clindamycin is 8, ciprofloxacin is 11, erythrornycin is 6, trimethoprim/sulfamethoxazo]e is 11 ,and cephalosporins, teicoplaninl, vancomycin, piperacillin/tazobactam, tetracycline are all 12. Conclusions The cefoxitin disk diffusion test can reliably predict mecA-mediated oxacillin resistant Staphylococcus aureus. It would be best to combine cefoxitin disk diffusion test and oxacillin MIC test to improve accuracy of detection of mecA-mediated oxacillin resistant coagulase-negative Staphylococcus.Furthermore, infections due to the non-mecA-mediated oxacillin resistant coagulase-negative Staphylococcus can be treated by penicillinase-stable penicillins, β-lactam/β-lactam inhibitor combinations, relevant cephems and carbapenems.