Objective To evaluate the molecular mechanism of proliferation and invasion inhibition in oral squamous cell carcinoma transfected with recombinant adenovirus-p53 (Ad-p53) .Methods Tca8113 cell lines were transfected with Ad-p53. Then the effect of p53 overexpression on cancer cells proliferation and invasion was observed. The expression of mitogen -activated protein kinase (MAPK) , serine/threonine kinase (AKT) signaling pathway related proteins, cell cycle and apoptosis related proteins Cyclin D1, P21 and Bcl-2 were detected by Western blotting analysis.Results After transfected with Ad-p53, the proliferation and invasion of Tca8113 cells were significantly inhibited (PConclusion The AKT signaling pathway may be a key molecular mechanism for proliferation and invasion inhibition of oral squamous cell carcinoma caused by p53. The protein of Cyclin D1, P21 and Bcl-2 may be the downstream targets of AKT signaling pathway. This may provide a new evidence for AKT pathway and downstream targets as a promising therapeutic target for malignant tumors.