Objective: To analyze the difference in circular RNA (circRNA) expression profiles between hepatocellular carcinoma (HCC) tissue and normal liver tissue. Methods: The circRNA expression profiles in 3 paired specimens of HCC tissue and its adjacent liver tissue were detected by using the human circRNA microarray. After preprocessing and homogenization of the original data, the differentially expressed circRNAs were searched out (the circRNA in HCC tissue showed a greater than 1.5-fold change which was also statistically significant compared with adjacent liver tissue and was regarded as differentially expressed circRNA). Then, after these circRNAs screening according to the principle of higher fold change and better consistency and their putatively targeting miRNAs prediction by bioinformatics software combined with literature review, the circRNAs that potentially contribute to HCC development were preliminarily identified. Results: The circRNA expression profile in HCC showed remarkable changes compared with adjacent hepatic tissue. In HCC tissue, a total of 82 circRNAs showed a greater than 1.5-fold change, and of them, 21 were up-regulated and 61 were down-regulated; a total of 3 circRNAs showed a greater than 5-fold change, and of them, 2 were up-regulated and 1 was down-regulated. The significantly up-regulated circRNA hsa-circ-0043278 (8.15 fold, P=0.002) and hsa-circ-0006220 (12.73 fold, P=0.033), and significantly down-regulated circRNA hsa-circ-0065214 (6.28 fold, P=0.019) were finally obtained after screening. Bioinformatics analysis and literature review suggested that hsa-miR-520 was potentially regulated by hsa-circ-0043278 and hsa-circ-0006220, which contributed to the occurrence and development of HCC. Conclusion: The circRNA expression profile in HCC is greatly changed. Hsa-circ-0043278 and hsa-circ-0006220 may play important roles in the occurrence and development of HCC.