Background: Vasculogenic mimicry (VM) is a new blood supply in malignant tumors and has long been considered as an effective factor in the metastasis and prognosis of many cancers. ALDH1 (a marker of cancer stem cells), Beclin1 (a biomarker of autophagy) and p16 (a suppressor gene of tumor) are all useful predictive factors for many cancer metastases. However, the prognostic and metastatic value of VM, ALDH1, Beclin1, or p16 in oral squamous cell carcinoma (OSCC) is unclear. In this study, we analyzed correlations among VM, ALDH1, Beclin1, and p16 in OSCC, and their respective associations with clinicopathological parameters and survival in OSCC. Methods: Positive rates of VM, ALDH1, Beclin1, and p16 in 186 whole OSCC specimens were detected by immunohistochemical and histochemical staining. Patients' clinical information was also collected. Results: Positive rates of VM, ALDH1, and Beclin1 were significantly higher, and levels of p16 were significantly lower in OSCC than in normal oral tissues. Positive rates of VM, ALDH1, and Beclin1 were positively associated with tumor grade, primary tumor (pT), lymph node metastasis (LNM), and tumor-node-metastasis (TNM) stage, and inversely with patients overall survival (OS) time. Levels of p16 was negatively associated with grade, pT, LNM, and TNM stage, and positively associated with smoking and alcohol. The p16+ subgroup had significantly longer OS time than did the p16-subgroup. In multivariate analysis, high ALDH1, VM, Beclin1 levels, tumor grade, pT, LNM, TNM stage, and low p16 levels were potential to be independent prognostic factors for OS time in OSCC patients. Conclusions: VM, and the expression of ALDH1, Beclin1, and p16 represent promising markers for metastasis and prognosis, and potential therapeutic targets for OSCC.