To explore the mechanism of triptolide in regulating cisplatin(DDP) resistance and angiogenesis in cervical cancer through microRNA-138-5p(miR-138-5p) and chromatin remodeling factor 1(RSF-1).Methods:In vitro experiments were conducted using human cervical cancer cells(HeLa)，human embryonic kidney cells(293T)，and human umbilical vein endothelial cells(HUVEC).HeLa/DDP-resistant cell lines were established.HeLa/DDP cells were randomly divided into cisplatin+HeLa/DDP group，triptolide+cisplatin+HeLa/DDP group，triptolide+cisplatin+miR-138-5p inhibitor+HeLa/DDP group，and triptolide+cisplatin+miR-138-5p inhibitor+si-RSF-1+HeLa/DDP group.The 293T cells were divided into NC mimic group and miR-138-5p mimic group.HUVECs were categorized into cisplatin+HUVEC group，triptolide+cisplatin+HUVEC group，triptolide+cisplatin+miR-138-5p inhibitor+HUVEC group，and triptolide+cisplatin+miR-138-5p inhibitor+si-RSF-1+HUVEC group.The proliferation rate，migration ability，levels of miR-138-5p and RSF-1 were measured，and the targeting relationship between RSF-1 and miR-138-5p，as well as its effect on tube formation，were verified.Results:Compared to the cisplatin+HeLa/DDP group，the proliferation rate and migration ability of the triptolide+cisplatin+HeLa/DDP group decreased at 24，48，and 72 h(all P<0.05).In the triptolide+cisplatin+HeLa/DDP group，miR-138-5p levels significantly increased while RSF-1 levels decreased(both P<0.05) compared to the cisplatin+HeLa/DDP group.In the triptolide+cisplatin+miR-138-5p inhibitor+HeLa/DDP group，miR-138-5p expression levels significantly decreased while RSF-1 levels increased(both P<0.05) compared to the triptolide+cisplatin+HeLa/DDP group.Compared with the triptolide+cisplatin+miR-138-5p inhibitor+HeLa/DDP group，the triptolide+cisplatin+miR-138-5p inhibitor+si-RSF-1+HeLa/DDP group showed no significant difference in miR-138-5p levels(P>0.05)，but RSF-1 levels significantly decreased(P<0.05).Co-transfection of RSF-1-WT with miR-138-5p mimic resulted in reduced luciferase activity compared to the NC mimic group.The number of tubular structures formed was significantly lower in the triptolide+cisplatin+HUVEC group than in the cisplatin+HUVEC group，and also decreased in the triptolide+cisplatin+miR-138-5p inhibitor+HUVEC group than in the triptolide+cisplatin+HUVEC group.Moreover，the number of tubular structures formed was significantly lower in the triptolide+cisplatin+miR-138-5p inhibitor+si-RSF-1+HUVEC group than in the triptolide+cisplatin+miR-138-5p inhibitor+HUVEC group(all P<0.05).Conclusion:Triptolide can improve DDP resistance and angiogenesis in cervical cancer cells，potentially through the miR-138-5p/RSF-1 pathway.