Objective To investigate the expressions of serine-threonine kinase (Akt)/ mammalian target of rapamycin (mTOR)/p70 S6K in oral squamous cell carcinoma (OSCC) and provide references for early diagnosis and prognosis evalua-tion of OSCC.Methods A total of 51 cases of OSCC, 10 cases of paracancerous mucosa, and 10 cases of normal oral mucosa were collected. The expressions of Akt/mTOR/p70 S6K in these cases were detected using the SP method of immunohisto-chemistry. The correlation between their expressions in OSCC was also analyzed.Results The positive expressions of p-Akt, p-mTOR, and p70 S6K in OSCC were significantly higher than those in normal oral mucosa and paracancerous mucosa. The expressions of p-Akt, p-mTOR, and p70 S6K in OSCC were not correlated with age, gender, and clinical stage; by comparison, these expressions were correlated with lymph node metastasis and pathological grade. Strong positive correlations were also observed between the expressions of p-Akt, p-mTOR, and p70 S6K in OSCC.Conclusion Akt/mTOR/p70 S6K signaling molecules exhibit active expressions in OSCC and may be implicated in the occurrence and development of OSCC.