Circular RNAs (circRNAs) are critical regulators in tumor initiation and development and participate in the pathological process of hepatocellular carcinoma (HCC). However, the specific role and mechanism of circRNA, hsa_circ_102559, in HCC remains elusive. First, analysis of HCC-related circRNA expression profile GSE97332 and HCC patients showed a significant upregulation of hsa_circ_102559 in HCC tissues. Upregulation of hsa_circ_102559 in HCC cells was associated with the metastatic properties. Second, hsa_circ_102559 significantly promoted HCC metastasis, while knockdown of hsa_circ_102559 reversed the promotive effects on HCC progression. Functionally, hsa_circ_102559 could target and colocalize with miR-130a-5p in the cytoplasm of HCC cells. Annexin A2 (ANXA2) was identified as a target gene of miR-130a-5p, and overexpression of ANXA2 counteracted with the suppressive effects of hsa_circ_102559 silence on HCC metastasis. Lastly, xenograft experiment was established and results indicated that knockdown of hsa_circ_102559 inhibited HCC growth and metastasis through the downregulation of ANXA2. In conclusion, hsa_circ_102559 inhibited HCC progression via sponging miR-130a-5p to reduce ANXA2 expression, suggesting that hsa_circ_102559 might be a potential biomarker or therapeutic target for HCC.