This　study　is　to　investigate　the　relationship　between　ectonucleoside　triphosphate　diphosphohydrolase　5　(ENTPD5)　expression　and　lung　cancer　clinicopathological　factors,　and　the　impact　of　ENTPD5　on　lung　cancer　cell　functions.　Lung　cancer　specimens　and　matched　adjacent　normal　tissues　were　obtained　from　patients　without　any　preoperative　radiotherapy　or　chemotherapy.　Knockdown　of　ETNPD5　expression　led　to　significantly　decreased　lung　cancer　cell　growth　rate,　markedly　increased　apoptosis　and　the　ability　to　repair,　and　significantly　reduced　invasion.　Gene　chip　tests　showed　that　knockdown　of　ENTPD5　expression　caused　more　Caspase　expression.　Quantitative　real-time　polymerase　chain　reaction　showed　that　the　Caspase　3　expression　was　significantly　increased　after　the　knockdown　of　ENTPD5.　In　addition,　immunohistochemistry　showed　that　the　tumor　growth　marker,　proliferating　cell　nuclear　antigen,　was　significantly　reduced　in　the　knockdown　model.　Tumorigenicity　assay　and　terminal　deoxynucleotidyl　transferase-mediated　dUTP　nick-end　labeling　assay　showed　that　the　apoptosis　of　lung　cancer　cells　was　increased　in　the　knockdown　model.　Our　results　suggest　that　ENTPD5　affects　lung　cancer　apoptosis　via　Caspase　3　pathway,　and　can　be　potentially　used　to　monitor　prognosis　or　to　guide　appropriate　therapeutic　regimens.