Extensive analyses of clinical data indicate LncHIFCAR level is substantially upregulated in oral carcinoma, significantly associated with poor clinical outcomes and representing an independent prognostic predictor. Overexpression of LncHIFCAR induces pseudo-hypoxic gene signature, whereas knockdown of LncHIFCAR impairs the hypoxia-induced HIF-1a transactivation, sphere-forming ability, metabolic shift and metastatic potential in vitro and in vivo. Mechanistically, LncHIFCAR forms a complex with HIF-1a via direct binding and facilitates the recruitment of HIF-1a and p300 cofactor to the target promoters. Patients with high LncHIFCAR expression level had a significantly worse overall survivaland recurrence-free survival than those with low LncHIFCAR expression.