There are 48 members of the GP63 protease family in Trichomonas vaginalis according to our annotations; 37 of them are predicted to be transmembrane proteins. Because the GP63 protease family is the largest surface protease family and the second largest surface protein family, they are most likely to be involved in the interactions between T. vaginalis and the host cell surfaces, or otherwise participate in infection. We performed a preliminary study on the functions of GP63 in T. vaginalis (TvGP63). We demonstrated the cell surface localization of one highly expressed member of TvGP63 using indirect immunofluorescence assays in both isolate T016 and isolate 30236. The specific inhibitor of TvGP63 protease, 1,10-phenanthroline, was found to significantly inhibit the destruction of HeLa cells, whereas another chelator, EDTA, could not. Further tests showed that 1,10-phenanthroline did not inhibit the adherence of T. vaginalis cells to HeLa cells. The results presented in here suggest that GP63 protease plays a vital role in T. vaginalis infection process, but may not be related to the adherence of parasitic cells to their hosts.