Introduction: Carvacrol is an essential oil derived from oregano that is used as a natural additive to improve the efficiency of livestock nutrition. Residues of natural additives such as carvacrol should be monitored in food of animal origin to ensure consumer safety. The aim of this study was to appraise the quick, easy, cheap, effective, rugged and safe (QuEChERS) approach coupled with liquid chromatography and mass spectrometry as a means of carvacrol analysis in chicken tissue. Material and Methods: A 5 ± 0.05 g portion of plasma, lung, muscle and liver was mixed for 15 min with 5 mL of 1-butanol and 20 mL of water, then centrifuged. A 0.5 mL volume from the top layer was transferred, then 60 mg of octadecylsilane sorbent, 30 mg of primary and secondary amine and 200 mg of MgSO4 were added. The extract was mixed and centrifuged. The top layer was filtered and then transferred to an autosampler vial for analysis by high-performance liquid chromatography–tandem mass spectrometry. Results: The limit of detection was calculated at 0.06 μg g−1 and the limit of quantification was 0.2 μg g−1, with relative standard deviation repeatability and reproducibility below <20%. Conclusion: The validation results showed that this method could be a good alternative to determination of carvacrol by gas chromatography and is suitable for carvacrol analysis in different matrices.