The applications of biodiesel fuels to Diesel engines have attracted much attention in the past two decades, mainly due to its renewability, biodegradability, and reduced carbon emissions. However, biodiesel-powered engines tend to produce higher NOx emissions than Diesel engines. As the NOx emission regulations for the Diesel engines have been significantly tightened in the past two decades, the NOx emission control for biodiesel engines remains a great challenge. To deal with excessive NOx emissions from biodiesel engines, urea-based selective catalytic reduction (SCR) systems, which have been widely utilized in NOx emission control for Diesel-powered ground vehicles, need to be exploited as well. Urea-based SCR systems are well-known for the tradeoff between NOx reduction efficiency and ammonia slip. The application of biodiesel fuel to SCR systems can significantly change the exhaust condition and thus make SCR design and control even more challenging. This paper presents a systematic nonlinear model predictive control (NMPC) method for a urea-based SCR system in biodiesel engine applications. In this paper, a proper urea dosing strategy is derived as the solution of an NMPC problem such that both NOx and ammonia emission requirements can be met simultaneously. Experimental and simulation studies suggested the need to increase SCR size for biodiesel applications. The effectiveness of proposed controller for biodiesel applications was successfully demonstrated in the simulation study. Such an NMPC-based SCR control strategy can be instrumental for reducing tailpipe emissions for flexible-fuel ground vehicles in the future.