Background and Aims Lymph node metastasis (LNM) is a major determinant of prognosis in patients with gallbladder carcinoma (GBC). Accurate preoperative assessment of LNM is essential for individualized treatment planning. This study investigated the predictive value of the inflammatory burden index (IBI) combined with hypoxia-inducible factor 1α (HIF-1α) for LNM and evaluated their interaction in patients with GBC.Methods Clinical data from 106 patients with pathologically confirmed GBC treated at Linyi Central Hospital between January 2020 and March 2025 were retrospectively analyzed. Patients were divided into an LNM group (n=44) and a non-LNM group (n=62) according to postoperative pathological findings. Differences in IBI and HIF-1α levels were compared between groups. Independent risk factors for LNM were identified using multivariate Logistic regression analysis. Receiver operating characteristic curve analysis was used to evaluate predictive performance. Regression discontinuity design (RDD) was applied to determine threshold effects. Additive and multiplicative interaction analyses were performed to assess the synergistic effects of IBI and HIF-1α. Subgroup analyses were conducted according to tumor differentiation and T stage.Results Patients with LNM exhibited significantly higher IBI and HIF-1α levels than those without LNM (both P<0.001). Multivariate Logistic regression analysis identified T stage, IBI, and HIF-1α as independent risk factors for LNM (all P<0.05). The combined model demonstrated good predictive performance with an area under the curve of 0.847 (95% CI=0.782-0.902), outperforming either marker alone. RDD analysis identified significant thresholds at IBI<33.21 and HIF-1α<9.65 pg/mL, below which the risk of LNM decreased significantly. Significant synergistic interactions between IBI and HIF-1α were observed on both additive and multiplicative scales. Subgroup analyses showed that the combined model maintained superior predictive performance across different differentiation grades and T stages, particularly in poorly differentiated tumors and T3-T4 stage disease.Conclusion Preoperative IBI and HIF-1α are independent predictors of LNM in GBC. Their combined assessment significantly improves predictive accuracy and demonstrates synergistic effects, providing a useful tool for preoperative risk stratification and individualized therapeutic decision-making for GBC patients.