Liver cancer primarily accounts for the majority of malignancies of the liver. MicroRNAs (miRNAs) are endogenous non-coding RNAs, which are important in tumorigenesis. Abnormal expression of microRNA-346 (miR-346) has been demonstrated in various types of human cancer, however, its expression and potential molecular mechanism in liver cancer remains to be elucidated. Expression levels of miR-346 in liver cancer cell lines were determined by quantitative polymerase chain reaction. The effect of miR-346 on proliferation was evaluated by an MTT assay; cell migration and invasion were evaluated by Transwell migration and invasion assays and target protein expression was determined by western blotting. The present study observed that miR-346 was upregulated in liver cancer cell lines. miR-346 overexpression promoted cell proliferation, migration and invasion in liver cancer cells and conversely, inhibition of miR-346 resulted in the opposite effects. Furthermore, F-Box and leucine rich repeat protein (FBXL)2 was identified as a direct target of miR-346. miR-346 promoted proliferation, migration and invasion of liver cancer via FBXL2. Overall, these findings demonstrated that miR-346 may act as a potential prognostic marker and therapeutic target against liver cancer in the future.