Background: Surgical wound infection is one of the common complications in patients after osteosarcoma resection. It is imperative to grasp the risk factors comprehensively. Therefore, this study aimed to explore the risk factors of wound infection and deeply analyze the correlation between risk factors and wound infection. Methods: The study subjects were 101 patients who underwent osteosarcoma resection between April 2018 and August 2021. The diagnosis of postoperative wound infection was confirmed by postoperative observation of the incision, ultrasound imaging, and pathogenic examination. This study included a series of potential factors, mainly laboratory examination indicators and patients' general information. The statistical methods had Pearson Chi-square test, Spearman-rho correlation test, multifactorial linear regression model, logistic regression analysis, and receiver operating characteristic (ROC) curve. Results: Pearson Chi-square test and Spearman correlation test showed that red blood cell (RBC) count (P = .033) and basic diseases (P = .020) were significantly correlated with a surgical wound infection after osteosarcoma resection. Logistic regression analysis manifested that basic disease (OR = 0.121, 95% CI: 0.015-0.960, P = .046) and RBC (OR = 0.296, 95% CI: 0.093-0.944, P = .040) have a clear correlation with whether the patients have surgical wound infection after osteosarcoma resection. And the interaction of basic diseases and RBC could diagnose the surgical wound infection sensitively and accurately (AUC = 0.700, P = .014, 95% CI = 0.564-0.836) via the ROC analysis. Conclusion: Patients with basic diseases and low RBC were risk factors for surgical wound infection after osteosarcoma resection.