〔Abstract〕 Objective To explore the effect and mechanism of lycorine on oxaliplatin(OXA) induced chemotherapy pain in mice. Methods 40 mice were randomly divided into 4 groups, 10 mice per group, which were respectively divided into control group, model group, administration group, and inhibitor group.A mouse model of chemotherapy induced pain was established by intraperitoneal injection of OXA for 5 consecutive days. Intrathecal administration of lycorine was performed. Behavioral changes and expression levels of inflammatory related proteins weredetected. Results Compared with control group, model group mice exhibited the increased number of spontaneous flinches, decreased mechanical nociceptive threshold, decreased movement distance and latency, and up-regulated expression levels of interleukin-1β(IL-1β), astrocytic marker glial fibrillary acidic protein(GFAP), cyclooxygenase-2(COX-2), NOD-like receptor protein 3(NLRP3), cysteinyl aspartate and specific proteinase 1(Caspase-1). Compared with model group, lycorine administration reduced the number of spontaneous flinches, increased mechanical nociceptive threshold, enhanced the movement distance and latency, bound and reduced COX-2 expression, down-regulated the expression levels of IL-1β, GFAP, NLRP3 and Caspase-1. Conclusion Lycorine reduces COX-2 expression, inhibits NLRP3 inflammasome activation, suppresses spinal inflammation, consequently alleviates pain behaviors and improved motor ability of mice.