Long noncoding RNAs (lncRNAs) are dysregulated in cancer and involved in oncogenic or tumor inhibitory processes. The aim of the study was to investigate the expression pattern of lncRNA XLOC_013703 in multiple myeloma (MM) and to evaluate its biological role and potential significance. We found that XLOC_013703 was significantly decreased in CD138 positive plasma cells and serum of MM patients compared to normal controls, and the decreased XLOC_013703 expression was correlated with β2‐MG, serum‐free light chain (s‐FLC) and revised international staging system. RNA‐fluorescence in situ hybridization results revealed that XLOC_013703 was distributed both in the nucleus and in the cytoplasm of MM cells including H929, RPMI8226, and U266. Overexpression of XLOC_013703 inhibited the proliferation of U266 cells and blocked the cell cycle in G1 stage, thus contributing to MM cell apoptosis. By contrast, knockdown of XLOC_013703 promoted the growth of H929 cells. Western blot analysis confirmed that the expression of p‐IκBα and nuclear P65 was substantially increased in shRNA transfection groups compared to control groups, whereas overexpression of XLOC_013703 reduced these expressions. In conclusion, we confirmed that the decreased expression of a novel lncRNA, XLOC_013703, in MM. XLOC_013703 was involved in MM cell survival and proliferation via nuclear factor‐κB pathway which represents a potential therapeutic target for MM. © 2019 IUBMB Life, 71(9):1240–1251, 2019