Pancreatic cancer (PC) is the seventh most common cause of cancer-associated mortality worldwide. The current study aimed to investigate the function and molecular mechanism underlying long non-coding (lnc)RNA SNHG15 in PC tissues and cells. Relative expression levels of lncRNA SNHG15, miR-345-5p and RAB27B in PC cells and tissues were examined by performing reverse transcription-quantitative PCR. The association between SNHG15, miR-345-5p and RAB27B was validated using a Dual-luciferase reporter assay. Proliferation, invasion and migration of PC cells were analysed by conducting MTT, wound healing and Transwell assays. Western blotting was performed to detect the relative expression of the RAB27B protein. The relative expression level of lncRNA SNHG15 and RAB27B was elevated, but that of miR-345-5p was decreased in PC. Silencing of SNHG15 suppressed the proliferation, invasion and migration of PC cells and suppressed tumour growth in xenograft mice . miR-345-5p was the target gene of SNHG15 and suppressed cell proliferation, migration and invasion in PC. Furthermore, miR-345-5p targeted RAB27B. The use of miR-345-5p inhibitor or overexpression of RAB27B reversed the suppressive effect of the small interfering RNA si-SNHG15-1 exerted on the proliferation, invasion and migration of PC cells. Silencing of SNHG15 inhibited the proliferation, invasion and migration of PC cells by mediating the miR-345-5p/RAB27B axis, thereby implying its potential as a prognostic marker and target for PC therapy.