Background:　Our　previous　work　showed　that　some　Rho　GTPases,　including　Rho,　Rac1　and　Cdc42,　play　critical　roles　in　gastric　cancer　(GC);　however,　how　they　are　regulated　in　GC　remains　largely　unknown.　In　this　study,　we　aimed　to　investigate　the　roles　and　molecular　mechanisms　of　Dock6,　an　atypical　Rho　guanine　nucleotide　exchange　factor　(GEF),　in　GC　metastasis.　Methods:　The　expression　levels　of　Dock6　and　miR-148b-3p　in　GC　tissues　and　paired　nontumor　tissues　were　determined　by　immunohistochemistry　(IHC)　and　in　situ　hybridization　(ISH),　respectively.　The　correlation　between　Dock6/miR-148b-3p　expression　and　the　overall　survival　of　GC　patients　was　calculated　by　the　Kaplan-Meier　method　and　log-rank　test.　The　roles　of　Dock6　and　miR-148b-3p　in　GC　were　investigated　by　in　vitro　and　in　vivo　functional　studies.　Rac1　and　Cdc42　activation　was　investigated　by　GST　pull-down　assays.　The　inhibition　of　Dock6　transcription　by　miR-148b-3p　was　determined　by　luciferase　reporter　assays.　Results:　A　significant　increase　in　Dock6　expression　was　found　in　GC　tissues　compared　with　nontumor　tissues,　and　its　positive　expression　was　associated　with　lymph　node　metastasis　and　a　higher　TNM　stage.　Patients　with　positive　Dock6　expression　exhibited　shorter　overall　survival　periods　than　patients　with　negative　Dock6　expression.　Dock6　promoted　GC　migration　and　invasion　by　increasing　the　activation　of　Rac1　and　Cdc42.　miR-148b-3p　expression　was　negatively　correlated　with　Dock6　expression　in　GC,　and　it　decreased　the　motility　of　GC　cells　by　inhibiting　the　Dock6/Rac1/Cdc42　axis.　Conclusions:　Dock6　was　over-expressed　in　GC　tissues,　and　its　positive　expression　was　associated　with　GC　metastasis　and　indicated　poor　prognosis　of　GC　patients.　Targeting　of　Dock6　by　miR-148b-3p　could　activate　Rac1　and　Cdc42,　directly　affecting　the　motility　of　GC　cells.　Targeting　the　Dock6-Rac1/Cdc42　axis　could　serve　as　a　new　therapeutic　strategy　for　GC　treatment.