Objective:To investigate the expression of microRNA-21 (miR-21) in colorectal cancer (CRC) tissues and cells,and investigate the inhibition of miR-21 on protein expression of PI3K/ PTEN/AKT/ mTOR signaling pathway,and look for the target genes which may be regulated by miR-21. Methods:The expressions of miR-21 and PTEN from tissues of CRC were detected by real-time fluorescence quantitative PCR (FQ –PCR) and immunohistochemistry (IHC). The anti-sense oligonucleotide (ASO) technology was performed to inhibit and verify the expression of miR-21 in HCT116 cells. The changes in PTEN,PI3K,Akt,MMP-9 and mTOR protein expressions were detected by Western blotting. The potential target gene prediction was performed by Bioinformatics. Dual luciferase report gene assay was performed to identify the activity of PTEN. Results:The expression level of miR-21 was increased in CRC tissue (P < 0.05),and the expression of PTEN was decreased in CRC tissue (P < 0.05). However,the expression level of miR-21 was negatively associated with PTEN expression (r = -0.396,P < 0.05). The level of miR-21 was the highest in HCT116 cell and lowest in SW480 cell. The expression of miRNA-21 in HCT116 cell lines was significantly inhibited,the expression of PTEN protein was significantly increased and the expressions of PI3K,Akt,MMP-9 and mTOR were down-regulated. PTEN was identified as one of target genes of miR-21 in CRC cell. Conclusion:PTEN,as one of target genes of miR-21 in CRC cell,can regulate the process of CRC. miR-21 expression is increased in CRC,and promotes cancer cell invasion and metastasis by inhibiting PTEN.