Liver cancer is one of the most common malignant human tumors with the highest morbidity and mortality rates of all cancer types in China. Evidence suggests that long non-coding RNA prostate cancer-associated transcript 6 (PCAT6) plays an essential role in tumor progression. However, the roles and mechanism of PCAT6 in liver cancer remain unclear. The present study showed that the expression of PCAT6 and heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) was upregulated in liver cancer tissues compared with non-cancerous tissues and were associated with poor overall survival time, whereas microRNA (miR)-326 expression was downregulated. Moreover, knockdown of PCAT6 significantly inhibited the proliferation and invasion of liver cancer cells and . A dual-luciferase reporter gene assay demonstrated that PCAT6 could bind to miR-326 and that hnRNPA2B1 was a direct target gene of miR-326. Mechanistically, silenced PCAT6 suppressed the malignant phenotype of liver cancer cells through upregulating the inhibitory effect of miR-326 on hnRNPA2B1 expression. Taken together, these data demonstrated that knockdown of PCAT6 inhibited liver cancer progression through regulation of the miR-326/hnRNPA2B1 axis, suggesting that PCAT6 functions as an oncogene and may be a useful biomarker for the future diagnosis and treatment of liver cancer.