ObjectiveTo develop a web-based machine learning server to predict lateral lymph node metastasis (LLNM) in papillary thyroid cancer (PTC) patients.MethodsClinical data for PTC patients who underwent primary thyroidectomy at our hospital between January 2015 and December 2020, with pathologically confirmed presence or absence of any LLNM finding, were retrospectively reviewed. We built all models from a training set (80%) and assessed them in a test set (20%), using algorithms including decision tree, XGBoost, random forest, support vector machine, neural network, and K-nearest neighbor algorithm. Their performance was measured against a previously established nomogram using area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), precision, recall, accuracy, F1 score, specificity, and sensitivity. Interpretable machine learning was used for identifying potential relationships between variables and LLNM, and a web-based tool was created for use by clinicians.ResultsA total of 1135 (62.53%) out of 1815 PTC patients enrolled in this study experienced LLNM episodes. In predicting LLNM, the best algorithm was random forest. In determining feature importance, the AUC reached 0.80, with an accuracy of 0.74, sensitivity of 0.89, and F1 score of 0.81. In addition, DCA showed that random forest held a higher clinical net benefit. Random forest identified tumor size, lymph node microcalcification, age, lymph node size, and tumor location as the most influentials in predicting LLNM. And the website tool is freely accessible at http://43.138.62.202/.ConclusionThe results showed that machine learning can be used to enable accurate prediction for LLNM in PTC patients, and that the web tool allowed for LLNM risk assessment at the individual level.