Background: Machine learning methods showed excellent predictive ability in a wide range of fields. For the survival of head and neck squamous cell carcinoma (HNSC), its multi-omics influence is crucial. This study attempts to establish a variety of machine learning multi-omics models to predict the survival of HNSC and find the most suitable machine learning prediction method. Results: For omics of HNSC, the results of the six models all showed that the performance of multi-omics was better

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... n each single-omic alone. Results were presented which showed that the BN model played a good prediction performance (area under the curve [AUC] 0.8250) in HNSC multi-omics data. The other machine learning models RF (AUC = 0.8002), NN (AUC = 0.7200), and GLM (AUC = 0.7145) also showed high predictive performance except for DT(AUC = 0.5149) and SVM(AUC = 0.6981). And the results of a vitro qPCR were consistent with the Random forest algorithm. Conclusion: Machine learning methods could better forecast the survival outcome of HNSC. Meanwhile, this study found that the Bayesian network was the most superior. Moreover, the forecast result of multi-omics was better than single-omic alone in HNSC.