Multiple myeloma (MM) is a cytogenetically heterogeneous malignancy of plasma cells in bone marrow. Among the cytogenetic abnormalities of MM, del(17p) is a well-recognized high-risk genetic lesion associated with the late stage and progression of the disease. MicroRNA (miR)-324-5p, located at 17p13.1, was identified to be involved in the dysregulation of a number of types of malignant disease. However, whether miR-324-5p is associated with the development and progression of MM remains unknown. In the present study, the expression status of miR-324-5p in MM, and its effect on the migratory and invasive ability of MM cells were investigated. Using ubiquitination pathway polymerase chain reaction array, the inhibitory effect of miR-324-5p on the ubiquitinated proteins was investigated. It was identified that miR-324-5p levels were decreased in samples from patients with MM and MM cell lines. Increased expression of miR-324-5p by transfection of miR-324-5p mimic suppressed the proliferative, migratory and invasive abilities of MM.1R cells. Furthermore, increased expression of miR-324-5p in MM.1R cells inhibited the ubiquitination pathway and decreased the levels of ubiquitination-associated proteins, particularly the Skp1-Cullin1-F-box -transducin repeat-containing protein (SCF-TrCP) E3 ligase. In addition, the results of the present study demonstrated that the SCF-TrCP E3 ligase may contribute to the suppression of MM cell motility by inhibiting the expression of metastasis-associated genes, including metastasis suppressor 1. In conclusion, the results of the present study suggested that miR-324-5p may act as a tumor suppressor by impairing the motility of MM cells by suppressing the ubiquitination pathway.