Purpose <p>Surgical site infection (SSI) is a serious complication of spinal instrumentation surgery. Various risk factors, including nutrition, immunity, and inflammation, have been reported. Recently, similar variables have been reported to help predict cancer prognosis. This study aimed to determine whether cancer prognostic factors are useful in predicting the occurrence of SSI in spinal instrumentation surgery, given the overlap between the factors associated with cancer progression and SSI occurrence.</p> Methods <p>We retrospectively analyzed 451 out of 828 patients who underwent spinal instrumentation surgery between 2013 and 2021. The patients were divided into an SSI group (Group I) and a non-SSI group (Group N). Blood samples collected within 3 months before surgery were used to examine the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), lymphocyte-C reactive protein (CRP) ratio (LCR), and modified Glasgow prognostic score (mGPS). Univariate and multivariate logistic regression analyses were used to identify independent predictors.</p> Results <p>SSI occurred in 12 patients (2.6%). Univariate analysis showed significant differences in PNI, NLR, LCR, and mGPS between groups. Multivariate analysis showed that only mGPS (odds ratio [OR] = 2.72, 95% confidence interval [CI] 1.45–5.11, <i>p</i> = 0.0019) was an independent predicting factor. Receiver operating characteristic curve analysis showed a cutoff value of 1 for the mGPS (AUC = 0.723).</p> Conclusions <p>mGPS was a significant independent predictive factor for SSI after spinal instrumentation surgery. Since mGPS is based on serum albumin and CRP levels, optimizing preoperative nutritional status and management of CRP levels are crucial for preventing SSI.</p>