MicroRNAs (miRNA) are small RNA molecules that have emerged as important regulators of gene expression in hepatocellular carcinoma (HCC). However, the expression, function and mechanism of miR-1251-5p in HCC remain poorly understood. In the present study, it was observed that miR-1251-5p expression was upregulated in HCC. Furthermore, higher miR-1251-5p level was correlated with poor prognosis, large tumor size, vascular invasion and high tumor-node-metastasis (TNM) stages of HCC patients. Functionally, miR-1251-5p drove HCC cell proliferation, migration and invasion in vitro, and promoted growth and metastasis of HCC cells in vivo. A-kinase anchor protein 12 (AKAP12) was screened as a direct target of miR-1251-5p by using the starBase V3.0 online platform. The AKAP12 mRNA expression was downregulated and negatively correlated with miR-1251-5p level in HCC tissues. Furthermore, in vitro experiments confirmed that AKAP12 was targeted and negatively regulated by miR-1251-5p. Importantly, AKAP12 overexpression decreased HCC cell proliferation, migration and invasion, whereas inhibition of AKAP12 rescued the miR-1251-5p knockdown-attenuated HCC cell proliferation, migration and invasion. Overall, the present study indicates that miR-1251-5p plays an oncogenic role in HCC by targeting AKAP12, and may be a potential therapeutic target for HCC treatment.