To explore the mechanism of Shanjia Baihua Decoction combined with gemcitabine in combating drug resistance in pancreatic cancer.Methods:Thirty mice were randomly divided into a model group,a gemcitabine group,and a combination group.A subcutaneous tumor transplantation model was established in mice.Mice were treated with Shanjia Baihua Decoction,gemcitabine,or Shanjia Baihua Decoction and gemcitabine in combination.Changes in tumor volume and weight were observed,along with the steroid receptor coactivator(Src)/inhibitor of differentiation(Id1) signaling pathway proteins.The human pancreatic cancer cell line PANC-1 was divided into control,gemcitabine treatment,combination treatment,combination+miR-124-3p inhibitor,and combination+overexpressed SDF2L1 groups.Cell proliferation and migration abilities,as well as levels of miR-124-3p,SDF2L1,and mRNA were compared.Results:Compared to the gemcitabine group,the combination group exhibited reduced tumor volume and weight,and decreased levels of Id1 and p-Src/Src,and SDF2L1.Compared to the control group,the gemcitabine treatment group showed significantly reduced cell proliferation and migration rates,increased miR-124-3p levels,and decreased SDF2L1 levels.Compared to the gemcitabine treatment group,the combination group further reduced cell proliferation and migration rates,elevated miR-124-3p,and decreased SDF2L1 levels.Compared to the combination group,the combination+miR-124-3p inhibitor group and the combination+overexpressed SDF2L1 group showed significantly increased cell proliferation and migration rates,and elevated SDF2L1 levels.Conclusion:Shanjia Baihua Decoction combined with gemcitabine exerts its anti-drug resistance effect in pancreatic cancer by upregulating miR-124-3p to inhibit SDF2L1.