Objective: To discuss the effect and molecular mechanism of mi R-146 a on the proliferation of lung cancer cells by targeting and regulating the macrophage migration inhibitory factor(MIF) gene. Methods: RT-PCR was employed to detect expression of mi R-146a; immunohistochemistry was used to detect the expression of MIF. The luciferase reporter gene technique was adopted to verify that MIF was the specific reverse target gene of mi R-146 a and the liposome LipofectamineTM2000 was employed to transfer the modeled mi R-146 a mimics, and mi R-146 a negative control(NC) in NSCLC cells to detect the expression of MIF m RNA and protein. MTT assay was used to detect cell viability, cloning technique to detect cell proliferation ability, Annexin V-PI to detect cell apoptosis, UV spectrophotometry to detect viability of cysteinyl aspartate specific proteinase 3(Caspase 3), and western blot to detect expression of nuclear factor-κB(NF-κB) in cells. Results: The expression of mi R-146 a in NSCLC lung tissues was lower than that in the normal lung tissues besides the lung cancer; while the expression of mi R-146 a in NSCLC cells was lower than that in normal human embryonic lung tissues. It was chosen as the subsequent cell line for its appropriate expression in A549. The expression of MIF protein in NSCLC lung tissues was higher than that in the normal lung tissues besides the lung cancer. The luciferase reporter gene proved that MIF was the reverse target gene of mi R-146 a. The mi R-146 a mimics were transfected into A549 cells through the liposome. Compared with NC group, the expression of MIF protein and m RNA was significantly decreased(P<0.01), with the decrease in the cell viability(P<0.01), the decrease in the number of clones(P<0.01), cell apoptosis(P<0.01), the increase in the activity of Caspase 3(P<0.01), and decrease in the phosphorylation of NF-κB p65(P<0.01). Conclusions: mi R-146 a has low expression in NSCLC tissues and cell lines, while MIF has the over expression in NSCLC tissues. The increased expression of mi R-146 a can inhibit the expression of MIF via the gene targeting and thus inhibit the proliferation of A549 cells and induce the apoptosis of cancer cells, which may be realized through NF-κB signaling pathway. Objective: To discuss the effect and molecular mechanism of mi R-146 a on the proliferation of lung cancer cells by targeting and regulating the macrophage migration inhibitory factor (MIF) gene. Methods: RT-PCR was employed to detect expression of mi R- 146a; immunohistochemistry was used to detect the expression of MIF. The luciferase reporter gene technique was adopted to verify that MIF was the specific reverse target gene of mi R-146 a and the liposome Lipofectamine ™ 2000 was employed to transfer the modeled mi R-146 a mimics, and mi R-146 a negative control (NC) in NSCLC cells to detect the expression of MIF m RNA and protein. MTT assay was used to detect cell viability, cloning technique to detect cell proliferation ability, Annexin V-PI to detect cell apoptosis, UV spectrophotometry to detect viability of cysteinyl aspartate specific protein 3 (Caspase 3), and western blot to detect expression of nuclear factor-κB (NF-κB) in cells. Results: The expression of mi R-146 a in NSCLC lung tissues was lower than that in the normal lung tissues besides the lung cancer; while the expression of mi R-146 a in NSCLC cells was lower than that in normal human embryonic lung tissues. It was chosen as the subsequent cell line for its appropriate expression in A549. The expression of MIF protein in NSCLC lung tissues was higher than that in the normal lung tissues in the lung cancer. The luciferase reporter gene proven that MIF was the reverse target gene of mi R-146 a. The mi R- Compared with NC group, the expression of MIF protein and m RNA was significantly decreased (P <0.01), with the decrease in the cell viability (P <0.01), the decrease in (P <0.01), the increase in the activity of Caspase 3 (P <0.01), and decrease in the phosphorylation of NF-κB p65 (P <0.01). Conclusions: mi R-146 a has a low expression in NSCLC tissues and cell lines, while MIF has the over exp ression in NSCLC tissues. The increased expression of mi R-146 a can inhibit the expression of MIF via the gene targeting and thus inhibit the proliferation of A549 cells and induce the apoptosis of cancer cells, which may be realized through NF-κB signaling pathway .