Background The potential role of circFNDC3B in regulating oral tongue squamous cell carcinoma development (OTSCC) remains unknown. Methods The level of circFNDC3B in OTSCC tissues or cell lines was measured and its function in vitro and in vivo was analyzed. Interactions among circFNDC3B, miR-1322, and MED1 were verified by luciferase reporter and RNA pull-down assays. Results The level of circFNDC3B in tissues or cell lines of OTSCC was higher than that in control groups. siRNA-mediated circFNDC3B inhibition resulted in weakened proliferation, migration, and invasion, which was reversed by miR-1322. Overexpression of MED1 in OTSCC cells partially reversed the tumor suppression functions of si-circFNDC3B or miR-1322 mimics in vitro. circFNDC3B overexpression dramatically promoted tumor growth in vivo. circFNDC3B directly bound with miR-1322 and consequently promoted the MED1 expression in OTSCC cells. Conclusions The circFNDC3B/miR-1322/MED1 axis participates in OTSCC progression, which may provide novel therapeutic targets for OTSCC.