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Long non-coding RNA RGMB-AS1 (lncRNA RGMB-AS1) was reported to play important roles in human cancer progression. However, the roles of lncRNA RGMB-AS1 in laryngeal squamous cell carcinoma (LSCC) remain unclear. In our research, lncRNA RGMB-AS1 was shown to be upregulated in LSCC tissues. High RGMB-AS1 expression was closely associated with advanced clinical features and poor prognosis. Silencing of lncRNA RGMB-AS1 suppressed LSCC cells proliferation and invasion in vitro and inhibited tumor growth in vivo. In mechanism, lncRNA RGMB-AS1 could sponge miR-22 to upregulate the expression of NLRP3. Additionally, we verified that the suppression of LSCC progression induced by lncRNA RGMB-AS1 reduction required the activity of miR-22. Altogether, these findings elucidated that lncRNA RGMB-AS1 could exert as an oncogenic factor through modulating miR-22/NLRP3 pathway, suggesting a potential novel target for the treatment of LSCC.