The effect of different hydroxyapatite particles on malignant melanoma cell was evaluated in vitro. Two kinds of short-rode hydroxyapatite particles, which range from 0.4 to 1 um and 0.5 to 1.5 um, were co-cultured with human’s malignant melanoma (MM) cell line A375 for 24, 48, and 72 h. Both of these HA particles showed the same cell proliferation rate as blank control, and there was no statistically significant correlation of matrix metalloproteinases-2 (MMP-2) expression to the HA particle size. SEM images showed that the membrane of tumor cell, which co-cultured with HA particles, was shrunk. The cell superficial sentus was reduced and small size particle’ effect was more obvious. Since immunohistochemistry and SEM data are qualitative technique, further precise methods might bring more information about the effect of HA particles on tumor behaviors. But this study can provide the bio-security test of micrometer HA particles in transplantation after tumor excision.