The extraction and quantitative determination of phenolic compounds (including phenolic acids, flavones, flavanols, alkaloid, tannins, procyanidins, and naphthoquinone) from the walnut kernel and its pellicle were performed by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Effective parameters on the tandem MS conditions, chromatographic conditions, and extraction solvents were evaluated and optimized. Under optimum condition, limits of detection and linearity were 0.000565–33.3 μg/g and 10–1000 ng/mL with r -values > 0.9952, respectively. The relative standard deviation from extraction recovery was from 74.27 ± 2.81% to 109.52 ± 4.33%, with precision values of < 15%. The proposed method was applied for simultaneous extraction and determination of phenolic compounds not only in the walnut kernel and its pellicle, but also in other tree nuts.