Pancreatic cancer has a 5-year survival rate below 10% and the treatment options are limited. Signal transducer and activator of transcription (STAT3) is a constitutively expressed protein in human pancreatic cancers and is associated with their poor prognosis. Targeting of STAT3 signaling using novel therapeutic agents is a potential strategy for pancreatic cancer treatment. Diarylidenylpiperidone (DAP) compounds， such as H-4073 and HO-3867， have been shown to be STAT3 inhibitors in several human ovarian cancers. Particularly， HO-3867 is an N-hydroxypyrroline derivative of DAP that has targeted cytotoxicity toward cancer cells without affecting healthy cells. In the present study， we evaluated the anticancer efficacy of H-4073 and HO-3867 in a human pancreatic cell line (AsPC-1). We found that both the compounds exhibited potential cytotoxicity to AsPC-1 cells by inducing G2/M cell-cycle arrest， apoptosis， and cell death， by mitochondrial damage and inhibition of STAT3 phosphorylation. In summary， H-4073 and HO-3867 are cytotoxic to AsPC-1 cells and seem to act through similar mechanisms， including STAT3 inhibition， cell-cycle arrest， and apoptosis.