Abstract: Objective To find antigens related with hepatocellular carcinoma (HCC). Methods Human Zinc Finger Protein 216 (ZNF216) was identified by SEREX(serological analysis of recombinant cDNA expression libraries, SEREX). The 6*His fusion protein of ZNF216 was obtained by synthesis bacterially and purified with a nickel affinity chromatography column. The level of anti-ZNF216 antibody in the sera was detected by ELISA，and ZNF216 mRNA level in HCC tissue and its peripheral normal tissue was detected by RT-PCR. Results The level of anti-ZNF216 antibody in the sera of HCC patients was higher than healthy individuals. ZNF216 mRNA level in HCC tissue is evidently higher than peripheral normal tissue. Conclusion The over-expression of ZNF216 in the HCC sera and tissue indicates that ZNF216 perhaps plays a role in HCC, but still needing more evidence.