Background <p>Tripartite motif-containing 44 (TRIM44) involves in various tumor development. This study investigated role of TRIM44 in multiple myeloma (MM).</p> Materials and methods <p>TRIM44 levels in bone marrow tissues and MM cell lines was detected by quantitative reverse transcription PCR (RT-qPCR). Cell viability, migration, and invasion of MM cells were evaluated under the interference of TRIM44 expression. The role of TRIM44 on regulating tumor growth in vivo was also investigated in subcutaneous tumor xenograft models. The protein interact between TRIM44 and Zinc Finger E-Box Binding Homeobox 1 (ZEB1) was also studied according IP followed by western blotting assay.</p> Results <p>TRIM44 was all highly expressed in collected bone marrow tissues and MM cell lines. Cell viability, migration, and invasion of MM cells with low expression of TRIM44 was significantly inhibited. Over-expression of TRIM44 can down-regulate the ZEB1 ubiquitination to enhance the protein stability.</p> Conclusions <p>TRIM44 exerts as an oncogenic factor to induce the oncogenesis of MM by stabilizing ZEB1.</p>