There has been increased interest in lignans due to their potential effect in reducing the risk of developing several diseases. To evaluate lignan contents, sensitive and accurate methods should be developed for their quantification in food. The present study aimed to validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of 5 lignans: lariciresinol (Lar), matairesinol (Mat), pinoresinol (Pin), secoisolariciresinol (Seco), and syringaresinol (Syr). The validation included selectivity, linearity, recovery, accuracy, and precision. The method was proved to be specific, with a linear response (R2≥0.99). The limits of detection were 0.040~0.765 μg/100 g and the limits of quantification were 0.114~1.532 μg/100 g. Recoveries were 90.588~109.053% for black sesame powder. Relative standard deviations of repeatability and reproducibility were below 5%. Total lignan contents of roasted coffee bean, oat, and blacksoy bean were 105.702 μg/100 g, 78.965 μg/100 g, and 165.521 μg/100 g, respectively. These results showed that LC-MS/MS analysis would be effective in producing acceptable sensitivity, accuracy, and precision in five lignan analyses.