Abstract: Distant metastasis of head and neck squamous cell carcinoma is a major challenge in clinical treatment. Once distant metastasis occurs, the five-year survival rate and healthy life expectancy of patients will be seriously affected. Distant metastasis is a complex pathologic process influenced by multiple factors. This has led to the fact that, despite the advances in multidisciplinary and comprehensive treatment modalities for head and neck squamous carcinoma, its global incidence is still on the rise, and the number of diagnosed cases and deaths in China is also increasing. Therefore, predicting patients' risk of metastasis and implementing aggressive preventive measures are crucial for effectively treating the disease and enhancing the likelihood of patient survival. Distant metastasis of head and neck squamous cell carcinoma involves numerous clinical and pathological indicators as well as abnormalities at the molecular level, and a systematic summary is still lacking. Therefore, the aim of this article is to review the clinicopathological factors and molecular markers associated with distant metastasis of head and neck squamous cell carcinoma, with a view to providing a scientific basis for risk assessment and individualized treatment strategies.