Panax notoginseng was used as material with exogenous Cd (0, 0.6, 3.0, 6.0, 9.0, 12 mg kg^-1, prepared with CdCl₂) and lime (0, 0.75, 1.5 t ha^-2, prepared with Ca(OH)₂) application to study the effect of cadmium stress on growth and saponins contents of P. notoginseng, the relative enzymes activities of saponins metabolism (SS, mevalonate kinase(MVK), P450, β-amyrin synthase (β-AS)) and protein expression used with iTRAQ proteome analysis technique to understand the response mechanism of P. notoginseng. The results showed the contents of soil available Cd and Cd contents in main root decreased under lime application. The available contents of soil Cd decreased by 9.2%-38.1% with 1.5 t ha^-2 lime application under Cd treatments. The biomass, root length, root surface area and root volume increased with lime application under Cd stress. The activities and expression levels of MVK, P450 and β-amyrin synthase decreased, resulting in decrease 8.6%-23.6% in saponins contents and ratio of Rg1 to Rb1. In general, the results indicate excessive application of lime would lead to a certain reduction in the content of saponin under Cd stress and inhibition of conversion of diol-saponins to triol-saponins with single-peak model to Ca/Cd ratio. It could be recommended that the ratio of Ca to Cd is less than 680 for reduction of cadmium content and maintaining saponin contents of main root of P. notoginseng for the production of high quality.