Abstract: In the engineering practice, merging statistical analysis into structural evaluation and assessment is a tendency in the future. As a combination of mathematical and statistical techniques, response surface (RS) methodology has been successfully applied to design optimization, response prediction and model validation. With the aid of RS methodology, these two serial papers present a finite element (FE) model updating and validation method for bridge structures based on structural health monitoring. The key issues to implement such a model updating are discussed in this paper, such as design of experiment, parameter screening, construction of high-order polynomial response surface model, optimization methods and precision inspection of RS model. The proposed procedure is illustrated by a prestressed concrete continuous rigid-frame bridge monitored under operational conditions. The results from the updated FE model have been compared with those obtained from online health monitoring system. The real application to a full-size bridge has demonstrated that the FE model updating process is efficient and convenient. The updated FE model can relatively reflect the actual condition of Xiabaishi Bridge in the design space of parameters and can be further applied to FE model validation and damage identification.