Hepatocellular carcinoma (HCC) is a leading cause of cancer-associated mortality worldwide. Despite clinical advances, the survival rate of patients with HCC remains low, as most patients are diagnosed with HCC when they are already at the advanced stage. Certain circular RNAs (circRNAs) are closely associated with the development of liver cancer. In the present study, a circRNA array was performed to screen differentially expressed circRNAs in HCC tissues. The further analysis focused on the newly identified circRNA_101237, the host gene of which, cyclin-dependent kinase 8, is located at chr13:26974589-26975761. CircRNA_101237 was determined to be upregulated in tumor tissue and serum of patients with HCC as compared with that in paracancerous tissues and the serum of healthy controls, respectively. In addition, the expression of circRNA_101237 was associated with tumor size, lymph node metastasis, distant metastasis and TNM stage. Univariate and multivariate analysis indicated that serum circRNA_101237 levels were an independent predictor of survival prognosis in patients with HCC. The overall survival of patients with high expression of circRNA_101237 was reduced compared with that of patients with low expression of circRNA_101237. Of note, cisplatin induced the expression of circRNA_101237 in HCC cells in a dose-and time-dependent manner in vitro, and the levels of circRNA_101237 in the serum of patients with cisplatin-resistant HCC and in cisplatin-resistant Huh7 cells were increased. The present study provided novel insight into the use of circRNA_101237 as a diagnostic biomarker for HCC and a potential therapeutic target.