Abstract: Objective：To study the effects of targeting FOXC2 inhibition on the angiogenesis of tongue cancer cell xenografts. Methods：Tca8113 tongue caner cells were injected subcutaneously into the nude mice in the right underside backs to establish xenograft models, and mice were divided into non-transfected group, mock control group, control group transfected with scrambled sequence plasmid, and interference group transfected with FOXC2-shRNA expression plasmid. Then, liposome-mediated plasmid transfection was done in the latter 3 group every 3 days. After mice were sacrificed, weight and size of xenografts were measured. Expression of FOXC2 protein was examined using western blot analysis. Microvessel parameters were detected using immunohistochemical staining. Results：Weight and size of xenografts, FOXC2 expression and microvessel parameters in interference group transfected with FOXC2-shRNA expression plasmid were less than the other three groups (P<0.05). Conclusions：Targeting FOXC2 inhibition could suppress the angiogenesis of tongue cancer cell xenografts, suggesting that it may become a potential therapy for tongue squamous cell cancer.