Multivariate adaptive regression splines (MARSP) is a nonparametric regression method. It is an adaptive procedure which does not have any predetermined regression model. With that said, the model structure of MARSP is constructed dynamically and adaptively according to the information derived from the data. Because of its ability to capture essential nonlinearities and interactions, MARSP is considered as a great fit for high-dimension problems. This chapter gives an application of MARSP in semiconductor field, more specifically, in standard cell characterization. The objective of standard cell characterization is to create a set of high-quality models of a standard cell library that accurately and efficiently capture cell behaviors. In this chapter, the MARSP method is employed to characterize the gate delay as a function of many parameters including process-voltagetemperature parameters. Due to its ability of capturing essential nonlinearities and interactions, MARSP method helps to achieve significant accuracy improvement.