The aim of this study is to reveal the response of highly malignant tumor cell to different hydroxyapatite particles. Human’s highly malignant melanoma (MM) cell line A875 is exposed to two kinds of short-rod hydroxyapatite particles. After incubated with hydroxyapatite particles at different time points, the effects of MM cell morphology, proliferation and invasion are evaluated by SEM, MTT, and MMP2 protein immunohistochemistry respectively. SEM figures show that superficial sentus of MM cells reduce; more secretion is found; and smaller HA particles have more obvious effect. At the same time, no statistic difference can be found in MTT assay and MMP2 expression measurement. This study also provides useful information about biosecurity of hydroxyapatite ceramic in transplantation after highly malignant tumor excision.