Nuclear protein‑1 (NUPR1) is a stress response factor that is important in the development of several human malignant tumor cells. However, the role of NUPR1 in multiple myeloma (MM) remains to be fully elucidated. In the present study, it was found that the mRNA levels of NUPR1 were significantly higher in specimens from patients with MM and MM cell lines (U266 and RPMI8226) than in cells of normal human bone marrow. The present study was undertaken to investigate the function of NUPR1 in the growth and apoptosis of MM cell lines. A lentivirus‑mediated short hairpin RNA was used to specifically inhibit the mRNA and protein expression of NUPR1 in the U266 and RPMI8226 MM cell lines. Flow cytometry and Cell Counting Kit‑8 assays were applied to examine the apoptosis and proliferation of U266 and RPMI8226 cell lines. The results revealed the inhibitory effect of NUPR1 silencing on the proliferation of U266 and RPMI8226 cells through inducing apoptosis, and arrest of cell cycle at the G0/G1 phase. Furthermore, NUPR1 silencing caused activation of caspase‑3,‑8 and‑9 and influenced specific gene expression, including an increase of phosphatase and tensin homolog (PTEN) and decrease of B‑cell lymphoma 2 and proliferating cell nuclear antigen. These findings showed that NUPR1 may be involved in the proliferation and apoptosis of MM cells by adjusting caspase proteins and PTEN, suggesting that NUPR1 may be a novel therapeutic target for MM.