Objective To investigate the effect of the down-regulation of A disintegrin and metalloproteinase 17 (ADAM17) on the killing effect of natural killer (NK) cells in non-small cell lung cancer (NSCLC).Methods Human NSCLC A549 cells were cultured in vitro and divided into normal control group (without transfection), negative control group (transfected with nonsense siRNA) and ADAM17 down-regulation group (transfected with ADAM17 siRNA). The mRNA level of ADAM17 in A549 cells was detected via quantitative real-time polymerase chain reaction (qRT-PCR), while the protein level of ADAM17 was determined via Western blotting (WB). NK cells were prepared and co-cultured with A549 cells of each group. The killing activity of NK cells was measured, and the protein levels of interferon-γ (IFN-γ), granzyme B (GraB) and perforin (PFP) were also detected via WB.Results The mRNA and protein levels of ADAM17, the protein levels of IFN-γ, GraB and PFP, and the killing activity of NK cells against A549 cells were different among the groups as a whole (P < 0.05). Specifically, there were no significant differences in the mRNA and protein levels of ADAM17, the protein levels of IFN-γ, GraB and PFP, or the killing activity of NK cells against A549 cells between normal control group and negative control group (P > 0.05), while the mRNA and protein levels of ADAM17, the protein levels of IFN-γ, GraB and PFP, and the killing activity of NK cells against A549 cells were lower in the ADAM17 down-regulation group compared with those in the normal control group and negative control group (P < 0.05).Conclusions The down-regulation of ADAM17 in NSCLC A549 cells can enhance the killing effect of NK cells.