Objective To study the molecular mechanism of Zhiyang Pingfu Decoction（ 止 痒平肤液） in the treatment of targeted drug-associated skin rash and pruritus based on network pharmacology and bioinformatics.Methods Through the Traditional Chinese Medicine Systems Pharmacology Database（ TCMSP） and Analysis Platform and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine（ BATMAN-TCM）

the components and targets in the compound were screened. The corresponding targets for epidermal growth factor inhibitor（ EGFRIs） class of targeted drugs were found in the Adverse Drug Reaction Target Classification System（ ADRe CS-Target）. The protein-protein interaction（ PPI） database was used to screen the interactions between proteins

and the network topology results were analyzed by Cytoscape 3. 2. 1 software. DAVID online tools were used to enrich the key target signal pathways to predict the possible molecular mechanisms of Chinese medicine. Results A total of 4355 targets of the components in Zhiyang Pingfu Decoction were screened out from TCMSP and BATMAN-TCM databases

and 368 targets of rash and pruritus were searched from ADRe CS-Target database. The PPI database was used to analyze the interaction of proteins

and 8 key effective targets were obtained after the network topology analysis by Cytoscape software

including epidermal growth factor receptor（ EGFR）

interleukin-6（ IL-6）

cytochrome C（ CYCS）

chemokine ligand 2（ CCL2）

phospholipase A2-IVA（ PLA2 G4 A）

L-type amino acid transporter-1（ SLC5 A7）

Mu-type opioid receptor gene（ OPRM1）

catechol-O-methyltransferase（ COMT）

of which IL-6 was the core target. Quercetin and luteolin may be the main active ingredients of the compound through the analysis of the component of the key targets. Pathway enrichment results showed that cytokine and cytokine receptor interaction was the main pathway of action. Conclusion Zhiyang Pingfu Decoction mainly plays a role in the treatment of targeted drug-related rash and skin itching by regulating IL-6-related inflammatory signaling pathway.