Extracellular matrix (ECM) degrading enzymes, including matrix metalloproteinases (MMPs), are critical for cartilage destruction in the progression of osteoarthritis (OA). Thus, identifying novel drugs, which suppress the synthesis of MMPs may facilitate the treatment of OA. The cytotoxicity of lycorine was determined using a CCK8 assay. The effects of lycorine on IL‑1β‑induced upregulation of MMPs and activation of mitogen‑activated protein kinase pathways were detected by western blot analysis and reverse transcription‑quantitative polymerase chain reaction. Hematoxylin and eosin staining and Safranin O staining were used to evaluate the effect of lycorine in a mouse anterior cruciate ligament transection model. In the present study, it was demonstrated for the first time, to the best of our knowledge, that lycorine (LY) suppressed interleukin‑1β (IL‑1β)‑induced synthesis of MMP‑3 and MMP‑13 in vitro. Molecular analysis revealed that LY abrogated the phosphorylation of c‑Jun N‑terminal kinase (JNK) and the activation of the nuclear factor (NF)‑κB signaling pathway caused by IL‑1β stimulation. In addition, in vivo experiments in a mouse anterior cruciate ligament transection model confirmed the protective role of LY on cartilage. Taken together, the data obtained in the present study demonstrated that LY suppressed the IL‑1β‑induced expression of MMP‑3 and MMP‑13 through inhibition of the JNK and NF‑κB pathways, suggesting that LY may be used as a potential drug for the treatment of OA.