OBJECTIVE: P27Kip1 is the one of the negative regulators of the cell cycle that plays an important role in regulating cell cycle and inhibiting cell proliferation by restraining cell in G1 phase. P27Kip1 downregulation maybe related to the occurrence of oral squamous cell carcinoma (OSCC). It was found that miR-155 significantly upregulated in OSCC tissue. Bioinformatics analysis revealed that miR155 may bind with the 3'-UTR of p27Kip1. This study investigated the role of miR-155 in regulating p27Kip1 and affecting Tca8113 cell proliferation, cycle, and apoptosis. PATIENTS AND METHODS: A total of 46 cases of OSCC patients received treatment in our hospital were enrolled to obtain tumor tissue. Another 25 normal oral mucosa samples were selected as control to detect the relationship between miR-155 and p27Kip1 expressions. Dual luciferase assay was adopted to confirm the targeted relationship between miR-155 and p27Kip1. Flow cytometry was applied to test cell apoptosis and cell cycle. CCK-8 assay was used to evaluate cell proliferation. Caspase-3 activity was detected by spectrophotometry. RESULTS: MiR-155 upregulated, while p27Kip1 declined in OSCC tissue compared with normal oral mucosa. Their expressions were related to TNM stage. MiR-155 targeted suppressed p27Kip1 expression. MiR-155 mimic and/or pEGFP-p27Kip1 transfection obviously declined p27Kip1 expression, blocked cell cycle in G1 phase, reduced cell proliferation, enhanced Caspase-3 activity, and increased cell apoptosis in Tca8113 cells. CONCLUSIONS: MiR-155 increased, while p27Kip1 reduced in OSCC tissue. Inhibition of miR-155 upregulated p27Kip1 expression, blocked cell cycle in G1 phase, weakened cell proliferation, and induced cell apoptosis.