The invention belongs to the field of mechanical design and provides a prediction method of flexible-packaging lithium-ion battery packaging stress. The prediction method includes five steps of firstly, determining a battery temperature profile; secondarily, determining a cell gas-generation model; thirdly, determining a packaging mechanical property degradation model; fourthly, determining a packaging stress model; fifthly, predicting the packaging stress. The status of only the packaging safety performance testing methods exist at present is changed, increase of gas generation, degradation of packaging material performance, increase of volume and the like of the flexible-packaging lithium-ion battery which are caused along with time change are all taken into consideration, the curve, changed along with time, of the obtained stress value can be achieved, the stress value at different time interval can be predicted, and thus, a powerful support for the mechanical design of the flexible-packaging lithium-ion batteries is provided.