AIM: To explore the mechanism of action and clinical significance of NLRC4 in multiple myeloma by analyzing the relative expression and clinical significance of NLRC4 mRNA in bone marrow fluid of patients with multiple myeloma (MM), so as to guide the formulation of disease treatment and the evaluation of clinical prognosis. METHODS: MMRF database and GTEx database were used to compare the expression and survival correlation of inflammatory bodies between myeloma patients and normal controls. Real-time fluorescent quantitative polymerase chain reaction (qPCR) was used to detect the expression of inflammatory bodies in bone marrow fluid of 26 newly diagnosed myeloma patients and 19 post-treatment myeloma patients and peripheral blood of 28 normal volunteers admitted to the First Affiliated Hospital of Anhui Medical University from January to September 2023. The mRNA expression differences of each inflammatory body and the correlation between NLRC4 inflammatory body expression and clinicopathologic features, inflammatory factor/chemokine expression of newly diagnosed patients were analyzed. RESULTS: Compared with the control group and the treatment group, the expression of inflammasome mRNA in the newly diagnosed group was increased except for NLRP3, and the expression of NLRC4 mRNA was significantly increased (P<0.01). The hemoglobin count, creatinine level and calcium ion level were linearly correlated with NLRC4 mRNA expression level in newly diagnosed patients (P<0.05). The mRNA expression levels of IL-18, CCL-3 and NLRC4 in newly diagnosed patients were linearly correlated (P<0.05). CONCLUSION: NLRC4 inflammatosomes are highly expressed in MM, and promote the occurrence and development of tumor by promoting the production and release of inflammatory cytokines/chemokines IL-18 and CCL-3, which is of great significance for the formulation of treatment plan and clinical prognosis evaluation of multiple myeloma.