In this investigation, the effects of blending microalgae biodiesel with silicon dioxide (SiO2) nanoparticles in a diesel engine are evaluated. For the study, test fuels (diesel, B20, B20n25, B20n50, B20n75, and B20n100) were prepared by blending pure diesel with microalgae biodiesel with the addition of SiO2 nanoparticles having particle sizes ranging from 25 to 100 ppm. A liquid-cooled, two-cylinder, four-stroke, compression ignition engine having a load range between 2 and 12 kW, fuel injection timing of 23° bTDC, and 16.5:1 compression ratio was chosen for this study. The results demonstrated that the test fuels enhanced the engine performance and declined emissions. Performance parameters such as brake thermal efficiency (BTE) and brake-specific fuel consumption (BSFC) were all improved by 1.6-4.8% and 8.55-15.33%, respectively, by the biodiesel containing SiO2 nanoparticles. At full engine load, emissions such as carbon dioxide (CO2), smoke opacity (BSN), and NOx declined by 1.8-9%, 6.2-21.4%, and 19-34% respectively. The study backs the use of SiO2 nanoadditives for better performance and lower emissions in diesel engines. Test results were analyzed by Taguchi and RSM method to find optimized conditions.