Surgical site infections (SSIs) post-thoracoscopic radical resection in lung cancer patients pose significant clinical challenges. This study aims to comprehensively identify the independent risk factors that influence the occurrence of SSIs following thoracoscopic radical resection for lung cancer. The study employed a retrospective analysis of 130 patients who underwent thoracoscopic radical resection for lung cancer. Inclusion and exclusion criteria were clearly defined, and ethical approvals were obtained. Patients were monitored for SSIs via clinical and biochemical markers, with data comprehensively gathered from electronic health records. Statistical analysis was rigorously conducted using SPSS v27.0, with methodologies including t-tests, Chi-square tests and logistic regression. The study aimed to identify independent risk factors for SSIs and incorporated a multidimensional assessment approach to provide robust, clinically relevant findings. Univariate analysis revealed surgical duration ≥3 h, non-usage of antibiotics, presence of diabetes and elevated levels of C-reactive protein (CRP) and procalcitonin (PCT) as significant correlates for SSIs. Multivariate analysis substantiated these factors as independent risk variables: surgery duration (odds ratio [OR] = 9.698, p < 0.05), presence of diabetes (OR = 6.89, p < 0.05), elevated CRP (OR = 7.306, p < 0.05) and elevated PCT (OR = 6.838, p < 0.05). Conversely, antibiotic administration served as a protective factor (OR = 0.572, p < 0.05). Surgical duration of 3 h or more, diabetes and elevated levels of CRP and PCT significantly heighten the risk for SSIs after thoracoscopic radical resection in lung cancer patients. Perioperative antibiotic administration acts as a protective factor. Clinicians should implement tailored preventative strategies to mitigate these identified risks.