In the traditional interaction factor method, only the elastic settlement of pile groups can be calculated, and the interaction factors are significantly greater than the real results. Using 3D numerical simulation method to fit the the load-settlement curve of a single pile, the elastic parameters of soil and pile-soil interface parameters are determined through the elastic and elasto-plastic analyses. Then by establishing a two-pile model, the influences of various parameters such as the load level on pile top, ratio of pile spacing to pile diameter, modulus ratio of pile to soil, modulus ratio of pile tip soil to surrounding soil, pile slenderness ratio and existence of the third pile between two piles on the interaction factors are analyzed, and a polynomial curve is used to fit the results. Based on the results of numerical analysis and field tests, a method using single pile load tests to calculate the elastic and elasto-plastic settlement of pile groups in the interaction factor method is proposed, and it is extended to compute the nonlinear settlement of pile groups. Analysis of an engineering case shows that the load-settlement curve computed by the proposed method agrees well with the measured one, and the proposed method can save a lot of computing time than the conventional numerical simulation and is suitable for the analysis and design of large-scale piled raft foundation with large pile spacings.