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Circular RNAs (circRNAs) have been reported to play important roles in human cancers. Circular RNA homeodomain interacting protein kinase 3 (Circ-HIPK3) was investigated to be involved in tumorigenesis. However, the functions of circ-HIPK3 in oral squamous cell carcinoma (OSCC) remain vague. The expression of circ-HIPK3, microRNA (miR)-381-3p and Yes-associated protein1 (YAP1) was detected by qRT-PCR or western blot. Cell proliferation, apoptosis, invasion and migration were measured by MTT assay, flow cytometry, or transwell assay. The dual-luciferase reporter assay was employed to test the target correlations miR-381-3p and circ-HIPK3 or YAP1. Murine xenograft model was established to conduct in vivo assay. Circ-HIPK3 was elevated in OSCC tissues and cell lines, and decrease of circ-HIPK3 suppressed OSCC cell proliferation, invasion, migration and induced apoptosis in vitro as well as inhibited tumor growth in vivo. Rescue assay indicated circ-HIPK3 silence mediated OSCC progression inhibition by sponging miR-381-3p, which was a target of circ-HIPK3. Furthermore, miR-381-3p directly interacted with YAP1 and miR-381-3p inhibition could attenuate YAP1 deletion-induced suppression on cell malignant biological behavior in OSCC. Meanwhile, co-expression analysis showed circ-HIPK3 could regulate YAP1 expression by competing for miR-381-3p. Circ-HIPK3 contributed to OSCC growth and development through regulating YAP1 expression by sponging miR-381-3p, indicating a promising therapeutic strategy for OSCC. [ABSTRACT FROM AUTHOR]