In order to solve the problems of low reliability and poor prediction accuracy in traditional building structure settlement monitoring, the author proposes a monitoring and analysis of high-rise building settlement deformation status based on nonlinear regression. The author collected and wirelessly transmitted building settlement information through various hardware devices such as sensors and GPRS communication modules. The monitoring data collected by sensors were compared and analyzed to determine the settlement situation of the building. An RBF neural network prediction model was constructed for possible settlement points. Then, the leapfrog algorithm is used to optimize the structural parameters of the RBF neural network. The experimental results show that this method can accurately evaluate the possible settlement of building structures in actual environments, and the prediction error is small, with a maximum relative error of 4.83 %, indicating good warning ability. This method achieved the best actual value fitting curve results, verifying its feasibility in settlement prediction. Subsequently, a more widely applicable settlement detection and prediction system for building complex structures will be established based on the proposed method, in order to promote its large-scale application.