Sinonasal mucosal malignant melanoma (SNMMM) is a rare disease. The aim of this study was to investigate the expressions of HER4 and CD44 in human SNMMM tissues and their relationship with the clinicopathological features and prognosis of patients. In total, 64 paraffin-embedded samples of SNMMM treated in our hospital from 29 December 1999 to 24 June 2011 were collected. HER4 and CD44 were detected in the tissues of SNMMM by immunohistochemistry. The differences in the HER4 and CD44 expressions in the tissues were evaluated and matched with clinicopathological parameters and the survival rate, respectively. The positive rates of the HER4 and CD44 expressions were 70.3 and 65.6%, respectively; the positive expression of HER4 was correlated with a positive expression of CD44 (P<0.05). The positive expression of HER4 was correlated with the prognosis of SNMMM patients (P<0.05). There was no significant correlation between a positive expression of CD44 and the prognosis of patients (P>0.05). The expressions of HER4 and CD44 were not significantly correlated with sex, age, pigment, tumor site, etc. (P>0.05). Our results further emphasize a correlation between HER4 and CD44 expressions in SNMMM tissues and point out that a positive HER4 expression might be an important factor in valuing the prognosis of patients with SNMMM.