Aimed at the prediction problem of deformation and settlement of high-rise building, according to the grey system theory, the paper took a settlement and observation project of high-rise building in Yangling demonstration zone as an example, predicted the observation data of the project by grey GM (1,1) model, and analyzed and compared the prediction results and the instance data. The results showed that the predictive value and measured values coincide well. The prediction accuracy is first class,which indicated that the grey model was used to forecast the settlement and deformation of high-rise building is effective.The result can provide the typical instance for the prediction of settlement and deformation of high-rise building and offer reference for the design and construction of engineering.