The aim of the present study was to determine impacts of different additives on fatty acid (FA) composition and total tocopherol content of cottonseed oil (CSO) during deep-frying process using a chemometric approach. A quarter-fractional factorial design (Q-FFD) with two levels and five factors was used for preparing the frying CSO blends. In the experimental design, additives were such as ascorbic palmitate, mixed tocopherols, dimethylpolysiloxane (DMPS), lecithin and sesame oil were used were used as factors. The effect of additives on FAs composition and tocopherol content was evaluated with normal distribution (ND) graphs during 10 hours frying at 170±5°C. The data were statistically assessed by one-way analysis of variance (ANOVA) at a significance level of p<0.05. The ANOVA test results were in good agreement with ND graphs and data indicated that the interaction between ascorbic palmitate and DMPS (A×C factor) showed a significant and protective effect on FAs. Meanwhile, the sesame oil (E factor) and A×C factor were showed a significant effect on level of tocopherols. The results of study indicated that present approach could be used to assess and improve the frying stability of any oil with respect to fatty acid composition and tocopherols. A c c e p t e d M a n u s c r i p t 2 Abbreviations CSO, cottonseed oil; Q-FFD, quarter-fractional factorial design; DMPS, dimethylpolysiloxane; ND, normal distribution; ANOVA, one way-analysis of variance; FAs, fatty acids; FAC, fatty acid composition; SFAs, saturated fatty acids; USFAs, unsaturated fatty acids; MUFA, monounsaturated fatty acids; PUFAs, polyunsaturated fatty acids; α-, β-, γ-and δ-Toc, alpha, beta, gamma and delta tocopherols; FAMEs, fatty acid methyl esters; GC-FID, gas chromatography-flame ionization detector; HPLC-FLD, high performance liquid chromatography fluorescence detector; ∑PUFA/∑SFA, total polyunsaturated to saturated fatty acids