Background: Propionibacterium acnes causes upregulation of inflammatory factors, such as cycloxygenase-2, prostaglandin E2, interleukin-1\beta, and tumor necrosis factor-alpha, increased levels of reactive oxygen species (ROS) and inward flow of calcium ions. This causes increased levels of the antimicrobial peptide LL-37 and inflammation of the skin, leading to redness, swelling, itching and other symptoms. Schisandra chinensis fruit oil (SCO) is rich in lignan active ingredients with various antioxidant and anti-inflammatory properties. Methods: In this study, SCO is obtained by supercritical CO{}_2 fluid extraction. SCO’s anti-inflammatory actions were investigated using P. acnes-induced inflammation HaCaT cells model. A method based on reversed-phase high-pressure liquid chromatography with a diode array detector was developed and validated for the simultaneous detection of five lignan components. Levels of inflammatory factors and LL-37 were measured by ELISA kit and western blot respectively. Ca{}^{2+} and ROS levels detected by flow cytometry. Results: The experimental results show that the contents of schisanol A, schisanol B, schisanin A, schisanin B, and schisanin C were 33.89 \pm 0.24, 14.89 \pm 0.45, 8.92 \pm 0.02, 29.14 \pm 0.67, and 4.74 \pm 0.09 mg/g, respectively. Studies have demonstrated that SCO can alleviate skin inflammation by inhibiting the COX-2/PGE2 and NF-\kappaB signalling pathway. In addition, SCO can inhibit ROS production, significantly block inward Ca{}^{2+} flow, alleviate cell damage, and modulate the content of the antimicrobial peptide LL-37. Conclusions: In summary, our study elucidated the anti-inflammatory activity of SCO in a cell model and provided a scientific basis for its application as a raw material in skin care.