In this paper, an extended Historical Data (HD) design was applied for evaluating the effect of an acetonized pyrolysis oil (PO) produced by pyrolysis of spent-car tires in coal. Experimental and statistical analyses were applied for examining the influence of some operating variables such as concentration of diesel oil (0, 10, and 20 L/t), pine oil (0.55, 0.1, and 1 L/t), and the pyrolysis oil (0, 10, and 20 L/t) as well as solid content of pulp (5, 10, and 15% (w/w)) on the yield and ash content of final concentrate. Fourier Transform Infrared Spectroscopy (FTIR) measurements showed that PO contained hydroxyl, aldehyde, aliphatic, and aromatic compounds. Based on the results of Analysis of Variance (ANOVA), the main effect of all variables, except concentration of pine oil, on the flotation responses were found significant. Batch flotation experimental results indicated that using pyrolysis oil resulted in a 2% increase in ash content and a 35% decrease of the yield, through a nonlinear trend. The curved behavior of flotation measures was due to the possible competitive adsorption between PO and diesel oil and nonselective interaction between pyrolysis oil and other reagents. The negative effect of PO on coal flotation efficiency was also ascribed to the interaction between hydrophilic groups in PO structure and the oxide nature of non-combustible materials of coal particles.