〔Abstract〕 Objective To investigate the effect of crocin on the growth, exercise and multi-organ injury of melanoma A375 cells, as well as the expression of proteins related to the AKT and STAT3 signaling pathways.Methods A subcutaneously transplanted tumor model of A375 nude mice was established. The mice were randomly divided into 4 groups, and the tumor was injected with 0, 20, 50, 100 mg/kg of crocin and normal saline respectively, and 0.1 ml each time to observe the changes of the tumor. Immunohistochemistry was used to detect the levels of Ki67,Caspase-3 and the expression of VEGF and Vimetin. The expression of Survivin and Bcl-2/Bax genes was detected by RT-PCR. The histopathological morphology of liver,lung and kidney was observed by HE staining. Western blot was used to detect the expression of motility and EMT markers E-cadherin,N-cadherin and Fibronectin,as well as phosphorylation of AKT and STAT3. Results Compared with the control group,the volume and weight of melanomas in the low,medium and high dose groups of Crocin decreased( P<0. 05); the number of Ki67,VEGF and Vimentin positive cells decreased( P<0. 05),while the number of Caspase-3 positive cells increased( P<0. 05); the expression of Survivin mRNA decreased( P<0. 05); the expression of Fibronectinprotein decreased( P<0. 05).Compared with the control group,the expression of Bcl-2/Bax mRNA in the middle and high dose groups decreased( P<0. 05); the expression levels of E-cadherin and N-cadherin decreased( P<0. 05); the phosphorylation levels of AKT and STAT3 decreased( P<0. 05); Crocin alleviated the tissue damage of liver,lung and kidney. Conclusion By inhibiting the phosphorylation of AKT and STAT3,Crocin can reduce the pathomorphological changes of liver,lung and kidney tissues,and inhibit the growth and movement of A375 melanoma,suggesting that saffron has a relieving effect on A375 melanoma. Saffron can be used as an effective and safe non-toxic regulator to prevent and treat melanoma.