〔Abstract〕 Objective To investigate the effects of gene interference with miR-105 on stem cell-like characteristics, malignant proliferation and invasion of non-small cell lung cancer cells. Methods RT-PCR was used to detect the expression level of miR-105 in lung tissues and adjacent tissues of 33 patients with lung cancer. After transfection of miR-105 inhibitor into A549 cells, the cells were randomly divided into three groups: Control group, inhibitor-NC group and miR-105 inhibitor group for follow-up experiments. The expression level of miR-105 was detected by RT-PCR. The pellet formation rate and pellet formation diameter were measured by pellet formation experiment. Western blot was used to detect the expression levels of SOX2 and OCT4 proteins. The number of CD133 positive cells was determined by flow separation. Cell proliferation was detected by clone formation assay. Transwell was used to detect cell invasion; Western blot was used to detect VEGF protein expression level. Results The results showed that the expression level of miR-105 in paracancer tissues was lower than that in cancer tissues. Compared with the Control group, miR-105 inhibitor group of miR-105 expression level decreased(P<0.05), the cells into a ball rate, into a ball diameter decreased(P<0.05), SOX2, OCT4 protein levels(P<0.05)and CD133 positive cells were lower(P<0.05), clone formation rate was lower(P<0.05), invasive cells were lower(P<0.05), VEGF protein levels were lower(P<0.05). Conclusion Gene interference with miR-105 can well inhibit stem cell-like characteristics, malignant proliferation and invasion of non-small cell lung cancer cells.