MicroRNAs (miRNAs) are abundant class of small noncoding RNA molecules (size less than 200 nucleotides) that regulate gene expression post-transcriptionally through complementary base pairing with mRNAs. They involve a variety of physiological, developmental, and pathophysiological processes. In recent years, increasing evidences revealed the contribution of microRNAs to the pathogenesis of many human diseases including liver, gallbladder, and pancreatic cancer. Moreover, miRNAs have been considered as useful non-invasive biomarkers that could be detected in the systemic circulation. By conducting miRNA expression profiling, the aberrant expression of miRNAs was discovered in cancer patient tissues. These aberrant expressions of miRNAs are closely correlated with disease status, drug resistance, and survival of cancer patients. Thus, targeting specific miRNAs could provide an efficient approach for the cancer therapy, indicating that targeting miRNAs combined with conventional anti-cancer therapy could be a promising therapeutic strategy to increase drug sensitivity and to achieve better therapeutic outcome. In this presentation, I summarize characteristics of miRNAs in liver, gallbladder, and pancreatic cancer and also briefly introduce in vitro and pre-clinical animal experiments for the miRNA-based therapeutic approaches.