Nowadays, the waste products as alternative fuels for diesel engines have become vital importance because of the increase in energy consumption, the rigid emission standards and the reduction in fossil fuel reserves. Waste tire pyrolysis oil is an important alternative fuel for the evaluation of waste. The aim of this study is to optimize the engine parameters which are responsible for the emission as well as engine performance analysis in terms of waste tire pyrolysis oil-diesel blends in a diesel engine by response surface methodology. Design of experiments was operated to design the count of tests. Injection pressure, fuel blending ratio and engine load have been chosen as the inputs, while brake thermal efficiency, nitrogen oxides, carbon monoxide and hydrocarbon have been chosen as the response parameters. Response surface methodology equations and response surface methodology optimizer were settled to estimate the values of brake thermal efficiency, carbon monoxide, hydrocarbon and nitrogen oxides and for making optimization. Outcomes represented that when the engine was operated with a load of 71.2121%, using 28.8889% waste tire pyrolysis oil ratio, and with an injection pressure of 225 bar, responses were determined to be best and the corresponding values of brake thermal efficiency carbon monoxide, hydrocarbon, and nitrogen oxides were 27.4075%, 0.0745%, 10.9851 ppm, and 519.6455 ppm, respectively. This study manifests that response surface methodology is an efficient and reliable virtual method for estimating the emission and performance values of a low power diesel engine using different fuel mixtures.