Abstract: Objective: To investigate the expression of circular RNA hsa_circ_0128298 in hepatocellular harcinoma (HCC) and evaluate its function in the growth process of HCC. Methods: qPCR was used to detect the expressions of hsa_circ_0128298 in 50 HCC tissues, corresponding paracancerous tissues and HCC cells. The effects of hsa_circ_0128298 on HCC growth was analyzed by CCK-8 kit, flow cytometry and western blot assays. The values of hsa_circ_0128298 for the diagnosis and prognosis of HCC were assessed by ROC curve and survival curve analyses. Results: Compared with the paracancerous tissues, the expression of hsa_circ_0128298 was significantly increased in HCC tissues ( U =846.0， P =0.005). The area under ROC curve (AUC^ROC) was 0.661, 95% confidence interval ( CI ) was 0.560 to 0.753, sensitivity was 80.0% and specificity was 50.0%. HCC patients with high expression of hsa_circ_0128298 displayed less overall survival time than those with low expression of hsa_circ_0128298 ( χ 2=6.294, P =0.012). RNA interference of hsa_circ_0128298 (si-hsa_circ_0128298) significantly inhibited HCC cell proliferation and induced cell cycle arrest at G0/G1, and also induced mRNA upregulation and protein expression of cyclin p21. Meanwhile，si-p21 partially reversed the proliferation inhibition and cell cycle arrest of HCC cells induced by si-hsa_circ_0128298, and restore its growth and proliferation potential. Conclusion: The highly expressed hsa_circ_0128298 in HCC could promote the growth of HCC by regulating the expression of p21 and promise to be a new target for diagnosis and treatment of HCC.