Objective To explore the cross-talk and miRNA-mRNA mechanism of Danggui Yinzi in the treatment of chronic urticaria though using GEO chip combined with network pharmacology, so as to provide theoretical basis for follow-up experimental research. Methods The difference of GSE57178 chip was analyzed by R language limma package, and the effective components, potential targets, PPI, KEGG, cross-talk and miRNA-mRNA mechanism of Danggui Yinzi were predicted and analyzed by TCMSP, TCMID, PubChem, String, DAVID and TargetScan database. Results 257 differential genes were identified by GSE57178 differential analysis, of which 240 genes were up-regulated (such as HIF1A, MMP12, STAT3, etc.), 17 genes were down-regulated (such as FABP7, KRT15, LGR5, etc.), among which 36 were potential targets for the treatment of chronic urticaria. Topological analysis showed that 24 key target genes played an important role. cross-talk analysis showed that one target(SELE)“cross talk” in the two pathways of TNF pathway and cell adhesion molecule (CAMs), one target (ITGB2)“crosstalk” in the two pathways of phagosome and CAMs, two targets (CTSL and CTSS)“cross talk” in the three pathways of antigen treatment expression, phagosome and lysosome, and two targets (VCAM1, ICAM1)“cross talk” in NF-kappaB, TNF and CAMs. One target(TLR4)“cross talk” in the three pathways of HIF-1, NF-kappaB and phagosome, and miRNA-mRNA predictive analysis showed that 24 potential targets mRNA, formed a 477 group of miRNA-mRNA patterns, which played a role in the inflammatory response of CU. Conclusion This study predicts and analyzes the multi-target, multi-cross-talk and multi-miRNA-mRNA mechanism of Danggui Yinzi in the treatment of CU from the genetic and molecular point of view, which provides a basis for follow-up research and can become a new direction of mechanism research in the future.