Objective To study the significance of metastasis associated genes nm23, p53 and S100A4 in the development of conjunctival melanoma metastasis. Methods Conjunctival melanoma tissue specimens were collected from 42 cases of conjunctival melanoma patients in Henan Eye Hospital from July 2015 to November 2016, meanwhile 30 cases of conjunctival nevus tissue samples served as control group under the informed consent.The expressions of nm23, p53 and S100A4 were detected in conjunctival melanoma group and control group by Western blot and immunohistochemical method.The relationship between the clinical and pathological features of nm23, p53 and S100A4 with conjunctival melanoma patients with lymph nodes metastasis were analyzed. Results Western blot assay showed that the expression level of nm23 in conjunctival melanoma group was lower than that in the control group , with a significant difference between them (P 0.05). There were siginificant differences in nm23, p53 and S100A4 protein expression positive rate between various sclera invasion groups and various distant metastasis groups (all at P<0.05). Conclusions Expression of nm23, p53 and S100A4 may play an important role in the invasion and metastasis of conjunctival melanoma, which may be the main reference index for the diagnosis and treatment. Key words: Conjunctival melanoma; nm23; p53; S100A4; Invasion; Metastasis