In this paper, the effects of the start of injection (SOI) timing and exhaust gas recirculation (EGR) rate on the nitrogen oxides (NOx) emissions of a biodiesel-powered diesel engine are studied with computational fluid dynamics (CFD) coupling with a chemical kinetics model. The KIVA code coupling with a CHEMKIN-II chemistry solver is applied to the simulation of the in-cylinder combustion process. A surrogate biodiesel mechanism consisting of two fuel components is employed as the combustion model of soybean biodiesel. The in-cylinder combustion processes of the cases with four injection timings and three EGR rates are simulated. The simulation results show that the calculated NOx emissions of the cases with default EGR rate are reduced by 20.3% and 32.9% when the injection timings are delayed by 2- and 4-deg crank angle, respectively. The calculated NOx emissions of the cases with 24.0% and 28.0% EGR are reduced by 38.4% and 62.8%, respectively, compared to that of the case with default SOI and 19.2% EGR. But higher EGR rate deteriorates the soot emission. When EGR rate is 28.0% and SOI is advanced by 2 deg, the NOx emission is reduced by 55.1% and soot emission is controlled as that of the case with 24% EGR and default SOI. The NOx emissions of biodiesel combustion can be effectively improved by SOI retardation or increasing EGR rate. Under the studied engine operating conditions, introducing more 4.8% EGR into the intake air with unchanged SOI is more effective for NOx emission controlling than that of 4-deg SOI retardation with default EGR rate.