Objective To understand the distribution and antimicrobial resistance of Staphylococcus spp. isolated from clinical specimens in Hunan Province from 2012 to 2021, provide scientific basis for rational clinical antimicrobial use as well as the formulation and evaluation of management policies for clinical antimicrobial use. Methods According to China Antimicrobial Resistance Surveillance System (CARSS) technical scheme, antimicrobial resistance of Staphylococcus spp. reported by Hunan Province Antimicrobial Resistance Surveillance System in 2012-2021 was analyzed with WHONET 5.6 software. Results From 2012 to 2021, the top 4 isolated Staphylococcus were Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus haemolyticus and Staphylococcus hominis. Staphylococcus spp. were mainly isolated from specimens of sputum, blood, secretion, wound pus, and urine. Sputum and blood specimens accounting for 25.4%-31.8% and 21.9%-27.8%, respectively. Among all clinically isolated bacteria, Staphylococcus spp. accounted for 15.5%-22.4%, showing a slowly downward trend. In the past 10 years, detection rates of methicillin-resistant Staphylococcus aureus (MRSA) decreased from 35.1% to 24.8%, while detection rates of methicillin-resistant coagulase negative Staphylococcus (MRCNS) increased, but were lower than 70%. Susceptibility rates of Staphylococcus spp. to vancomycin, teicolanin and linezolid were 100%. Conclusion Among clinically isolated Staphylococcus spp. in Hunan Province, the detection rate of MRSA has decreased. Vancomycin-, teicoplanin- and linezolid-resistant Staphylococcus spp. were not found. Management of rational use of antimicrobial agents as well as prevention and control of healthcare-associated infection should be strengthened continuously, and antimicrobial resistance surveillance should be conducted well.