Surgical site infection (SSI) has not been extensively studied in musculoskeletal tumors (MST) owing to the rarity of the disease. We analyzed incidence and risk factors of SSI in MST. SSI incidence was evaluated in consecutive 457 MST cases (benign, 310 cases and malignant, 147 cases) treated at our institution. A detailed analysis of the clinical background of the patients, pre- and postoperative hematological data, and other factors that might be associated with SSI incidence was performed for malignant MST cases. SSI occurred in 0.32% and 12.2% of benign and malignant MST cases, respectively. The duration of the surgery (P = 0.0002) and intraoperative blood loss (P = 0.0005) was significantly more in the SSI group than in the non-SSI group. We established the musculoskeletal oncological surgery invasiveness (MOSI) index by combining 4 risk factors (blood loss, operation duration, preoperative chemotherapy, and the use of artificial materials). The MOSI index (0-4 points) score significantly correlated with the risk of SSI, as demonstrated by an SSI incidence of 38.5% in the group with a high score (3-4 points). The MOSI index score and laboratory data at 1 week after surgery could facilitate risk evaluation and prompt diagnosis of SSI.