In our study, through in vitro and in vivo analyses, we first confirmed that LINC00261 could attenuate aerobic glycolysis in pancreatic cancer and revealed for the first time posttranscriptional regulatory mechanisms of LINC00261 acting as a ceRNA to sponge miR-222-3p and activate the HIPK2-mediated ERK/c-myc pathway and serving as a molecular decoy by sequestering IGF2BP1, which, in turn, decreased the mRNA stability of c-myc and thus reduced c-myc expression. This evidence concerns the gene HIPK2 and pancreatic neoplasm.