Abstract: Objective To explore the application value of preoperative neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammatory index (SII) in predicting inguinal lymph node metastasis of squamous cell carcinoma of the penis (SCCP). Methods A total of 99 patients with SCCP who were admitted to the Affiliated Hospital of Xuzhou Medical University from December 2008 to December 2021 were selected and their clinical data were retrospectively analyzed. According to the presence of inguinal lymph node metastasis, they were divided into two groups: a metastasis group (n=28) and a non-metastasis group (n=71). The univariate and multivariate logistic regression analyses were conducted to screen out the influencing factors of inguinal lymph node metastasis. The predictive efficacy of NLR, SII and their combination on inguinal lymph node metastasis was assessed by the receiver operating characteristics (ROC) curve. Results The levels of NLR and SII were significantly higher in the metastasis group than in the non-metastasis group. Multivariate logistic regression analysis indicated that low-degree differentiation (OR=9.839, 95%CI: 2.078-46.591), lymph-vascular space invasion (OR=8.845, 95%CI: 1.544-46.250), NLR (OR=2.838, 95%CI: 1.335-6.035), and SII (OR=1.003, 95%CI: 1-1.006) were the risk factors for inguinal lymph node metastasis of SCCP. The ROC analysis showed that the area under the curve (AUC) of NLR, SII, and both for predicting the inguinal lymph node metastasis of SCCP were 0.811, 0.772, and 0.851, respectively. The sensitivity was 0.893, 0.643, and 0.929, respectively. The specificity was 0.606, 0.845, and 0.648, respectively. Conclusions NLR and SII are effective predictors for inguinal lymph node metastasis of SCCP. NLR and SII alone and both have good efficacy in predicting inguinal lymph node metastasis of SCCP, which provide reference for preoperative evaluation of patients.