In the present work, the interaction between 2,5-dimethylfuran (2,5-DMF) and NO has been investigated. The study includes experimental and modeling data on the evaluation of the influence of the temperature, stoichiometry, and 2,5-DMF concentration on the NO conversion as well as on the 2,5-DMF conversion in the presence of NO. The experiments were performed in an isothermal quartz flow reactor at atmospheric pressure in the temperature range of 800–1400 K. Some of the results of the present work were compared to the experimental and modeling data from an earlier study on 2,5-DMF conversion under similar conditions but in the absence of NO. The results reveal that the temperature, stoichiometry, and 2,5-DMF concentration play an important role on the conversion of NO. Likewise, these variables also influence the 2,5-DMF conversion regime in the presence of NO.