Baicalein has been widely studied and showed a potent activity against pancreatic cancer in both in vivo and in vitro studies. Little is known regarding the effects of Skullcapflavone I (SFI), despite they have similar structures. So, this study was to explore the function of SFI on human pancreatic cancer. Panc-1 cells were transfected with miR-23a precursor, miR-23a inhibitor or the negative controls, and subsequently treated by SFI. Cell viability, Bromodeoxyuridine (BrdU)-positive cell rate, apoptosis, migration, invasion, and related protein expression were assessed by utilizing Cell Counting Kit-8 (CCK-8), BrdU staining, apoptosis assessment, transwell assay, and western blot. SFI significantly reduced the proliferation, migration, and invasion, as well as induced apoptosis of Panc-1 cells. MiR-23a, miR-21, and miR-155 were lowly expressed while miR-145 and miR-146a were highly expressed in SFI-treated cell. Of note, the antitumor effects of SFI were promoted by miR-23a suppression whereas attenuated by miR-23a overexpression. JAK/STAT and MAPK pathways were inhibited by SFI. Also, the pathway inhibition in SFI-treated cells was reversed by miR-23a overexpression. SFI might be a promising anti-pancreatic cancer agent by inhibiting cancer cells growth and motility. The anticancer activities of SFI might be through downregulation of miR-23a, as well as inhibition of JAK/STAT and MAPK pathways. K E Y W O R D S miR-23a, Panc-1 cell, pancreatic cancer, skullcapflavone I 1 | INTRODUCTION Pancreatic cancer, as one of the deadly diseases, has a 5-year survival rate of <7%. 1 As the rate of obesity, hyperlipidemia, diabetes, and chronic pancreatitis has exploded, the prevalence of pancreatic cancer is rising. In 2012, approximately 338,000 people had pancreatic cancer worldwide. 2 Pancreatic cancer is difficult to be diagnosed in an early stage since no symptoms usually appear; thus, a majority of patients present with