Electronic in-line pump system (EIPS) is an electronic controlled fuel injection system which meets China's emission regulations. In this paper, a numerical model of EIPS was developed in AMESim for the purpose of creating a tool for simulation experiments. Experiments were conducted at the same model conditions to validate the model. The results are quite encouraging and in agreement with model predictions which imply that the model can accurately predict the dynamic injection characteristics of EIPS. The design of experiments was performed using a 2-level-5-factor face-centered central composite design (FCCD) method in order to study the interactive effect of factors on fuel injection quantity fluctuation (FIQF). The factors studied were supply fuel pressure, cam linear velocity, control valve lift, needle spring pretightening force and nozzle flow coefficient. A quadratic response surface regression model was suggested according to the simulation experiments for FIQF prediction by means of partial least squares regression analysis. Coefficient of determination (R2) and leave-one-out cross-validation (Q2), normal distribution of standardized residuals and significance analysis were presented which demonstrate the significance of the model to predict FIQF of the system. Analysis of p-value for the model terms at 95% confidence level revealed that the interactive effects of cam linear velocity and control valve lift, cam linear velocity and needle spring pretightening force, cam linear velocity and nozzle flow coefficient, control valve lift and nozzle flow coefficient, needle spring pretightening force and nozzle flow coefficient had the most significant effects on FIQF, and then, the significant interactive effects on FIQF of the system were analyzed in detail. Research results of this paper can provide a theoretical guidance for fuel injection quantity(FIQ) stability design and optimization of EIPS.