Our study investigated whether microRNA-122 (miR-122) played important roles in the proliferation, invasion and apoptosis of human cholangiocarcinoma (CC) cells. QBC939 and RBE cells lines were chosen and divided into five groups: miR-122 mimic group, anti-miR-122 group, negative control (NC) group, mock group and blank group. MiR-122 expression was measured by qRT-PCR. Roles of miR-122 in cell proliferation, apoptosis and invasion were investigated using MTT assay, flow cytometer and Transwell invasion assay, respectively. MiR-122 expression was lower in CC tissues and QBC939 cell than that in normal bile duct tissues, HCCC-9810 and RBE cells. In both QBC939 and RBE cells lines, miR-122 expression was higher in miR-122 mimic group than that in NC group, mock group and blank group; opposite results were found in anti-miR-122 group. Cell proliferation and invasion were remarkably inhibited in miR-122 mimic group after 48 h/72 h transfection, while apoptotic cells numbers were much greater in miR-122 mimic group; the opposite results were obtained from antimiR-122 group (all P < 0.05). MiR-122 expression was significantly weaker in CC tissues, and miR-122 overexpression might play pivotal roles in inhibiting proliferation, stimulating apoptosis and suppressing invasion of CC cells, suggesting a new target for CC diagnosis and treatment.Cholangiocarcinoma (CC) is the second commonest primary liver malignancy after hepatocellular carcinoma (HCC) and is generally classified into three forms including intrahepatic cholangiocarcinoma (ICC), hilar cholangiocarcinoma and extrahepatic cholangiocarcinoma (ECC) 1 . CC is defined as a rare and fatal tumor, and the main challenge for treating CC is considered to be the accurate diagnosis at the early stage 2 . Incidence rate and mortality rate of ICC have steadily increased over the world in the past few decades while those of ECC decreased 3 . CC widely occurs in different regions with the highest in Southeast Asia and the lowest in Australia, and the rates are 96 per 100,000 in man and 38 per 100,000 in women 4 . The incidence rate is not controlled by improvements in diagnosis because the clinical characteristics of this cancer is not easy to identify 5 . Patients with respectable CC are usually recommended