Perineural　invasion　(PNI)　potentially　increases　the　risk　of　relapse　and　abdominal　pain　in　patients　with　pancreatic　ductal　adenocarcinoma　(PDAC).　However,　the　underlying　mechanisms　of　PNI　of　PDAC　is　incompletely　revealed.　Our　study　aimed　to　investigate　roles　of　miR-429　in　modulating　PNI　in　PDAC.　We　found　that　miR-429　was　downregulated　in　PDAC　cancer　tissues　and　was　profoundly　decreased　in　tissues　with　PNI.　It　was　reduced　in　nine　of　the　ten　examined　pancreatic　cancer　cell　lines.　MiR-429　mimics　restored　its　cellular　expressions　in　MIA　PaCa-2　and　BxCP3　cells　and　significantly　suppressed　cell　viability　and　invasion　of　the　cancer　cells.　The　online　bioinformatic　software　predicted　that　neurotrophin-3　(NT-3)　was　a　potential　target　gene　of　miR-429.　It　was　showed　that　NT-3　mRNA　elevated　in　PC　cancer　tissues,　especially　in　patients　presenting　PNI.　MiR-429　upregulation　substantially　suppressed　the　NT-3　mRNA　and　secretion　in　cancer　cells.　Also,　the　dual　luciferase　reporter　assays　confirmed　the　interaction　between　miR-429　and　NT-3.　When　co-culturing　the　two　PDAC　cells　with　PC-12 cells,　the　invaded　cell　counts　significantly　increased　comparing　with　the　sole　culture　of　cancer　cells.　However,　miR-429　mimic　transfection　or　NT-3　blocking　retarded　the　cancer　invasion　in　the　co-culture　system.　Besides,　we　found　that　cancer　cells　conditioned　medium　(CM)　treatment　significantly　increased　the　neurite　outgrowth　percentage　in　PC-12 cells,　which　was　suppressed　by　culturing　with　CM　from　miR-429　mimics-transfected　cells.　In　the　CM　cultured　PC-12 cells,　NT-3　receptor　TrkC　as　well　as　pain-related　proteins　TRPV1　and　TRPV2　significantly　elevated.　Collectively,　miR-429　potentially　suppressed　neurotrophin-3　to　alleviate　PNI　of　PDAC.