Background <p>Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) is an important antimicrobial-resistant organism in healthcare settings, and long-term surveillance is important for infection prevention and antimicrobial stewardship. Long-term epidemiological data on MRSA remain limited, particularly in cancer specialty hospitals. This study aimed to investigate the distribution and antimicrobial resistance trends of MRSA in a cancer hospital over a ten-year period (2015–2024).</p> Methods <p>We analyzed data from clinical isolates obtained at Sichuan Cancer Hospital between 2015 and 2024. Patient demographics, departmental sources, specimen information, hospital-acquired infection classification, and antimicrobial susceptibility testing results were collected. The epidemiological distribution and temporal trends in MRSA resistance were assessed over the study period.</p> Results <p>Among 13,829 hospitalization records with at least one positive culture, 1,550 <i>Staphylococcus aureus</i> isolates were identified. Of these, 433 were identified as MRSA (detection rate 27.94%). The MRSA detection rate initially increased, peaked at 35.48% in 2018, and then gradually declined; however, the interannual variations were not statistically significant. MRSA was detected across 23 departments. The highest number of MRSA isolates was detected in Surgery, particularly Head and Neck Surgery (54 isolates, 12.47%), followed by Radiotherapy, Internal Medicine, and other departments. Among MRSA detections classified as hospital-acquired infections, the largest number occurred in Head and Neck Surgery (31 cases, 20.95%). The Head and Neck Radiotherapy Ward and Thoracic Surgery Ward also had relatively high numbers of MRSA-associated hospital-acquired infections. The main infection sites among MRSA-associated hospital-acquired infections were the lower respiratory tract (60 cases, 40.54%) and surgical sites (32 cases, 21.62%). Regarding antimicrobial resistance, the resistance rates of MRSA to most tested antimicrobial agents did not show a clear increasing or decreasing trend. MRSA remained fully susceptible to daptomycin, linezolid, tigecycline, and vancomycin (all with 0% resistance). Exploratory analyses showed interannual differences in resistance rates for erythromycin, chloramphenicol, and moxifloxacin, but these findings should be interpreted cautiously.</p> Conclusion <p>This ten-year surveillance study in a cancer specialty hospital showed an average MRSA detection rate of 27.94%, with departmental heterogeneity in MRSA detection and in MRSA-associated hospital-acquired infections. Head and Neck Surgery accounted for the largest number of MRSA-associated hospital-acquired infections, whereas the Neurosurgery Ward had the highest MRSA detection rate. Antimicrobial susceptibility testing showed that resistance rates of MRSA to most agents remained stable. These findings may inform local empirical therapy, antimicrobial stewardship, and department-specific infection prevention strategies, but they should not be interpreted as direct evidence for individualized treatment decisions.</p> Clinical trial number <p>Not applicable.</p>