It is necessary to study the finite element (FE) modeling and updating in consideration of the model bias, because there are some model biases to affect the response prediction in the updated engineering structure. The FE model updating method with model bias is proposed, the model bias is quantified by the uncertainties of updating parameters in the method. Firstly, the optimization values of updating parameters are identified based on the response surface model and the model bias is obtained by comparing the simulation results and the test results. Secondly, the effect of model bias on updating parameters is identified by combining the response model and the sensitivity analysis, and then the updating parameters interval is obtained with model bias. Lastly, the proposed method has been validated by model updating on a cantilever beam. The updating results have proved the feasibility of the method. The results show that it can improve the reliability of the structural response predictions when the model biases are considered.