ObjectivesMicroRNAs play a role in the development and progression of head and neck squamous cell carcinomas (HNSCC). Our aim was to study the expression of miR‐26, miR‐107, miR‐125b, and miR‐203 in primary HNSCC with and without lymph node metastasis and their clinicopathological significance.Materials and MethodsThe expression of microRNAs in primary HNSCC with lymph node metastasis (n = 16) and their matched lymph node, as well as primary tumors without metastasis (n = 16), were determined by quantitative RT‐PCR and analyzed with clinicopathological features and survival.ResultsThe expression levels of miR‐26 (p < .05) and miR‐125b (p < .01) were higher in metastatic primary HNSCC, while levels of miR‐203 (p < .01) were lower. The expression of the microRNAs was associated with clinicopathological features, including miR‐26 high expression and N stage (p = .04), poor differentiation (p = .005) and recurrence (p = .007), miR‐125b high expression and N stage (p = .0005) and death (p = .02), and low levels of miR‐203 and N stage (p = .04). The high expression of miR‐26 was associated with shortened disease‐free survival, and high miR‐125b expression was an independent risk factor for poor disease‐specific survival.ConclusionsThese findings suggest that miR‐26 and miR‐125b may be associated with the progression and metastasis of HNSCC and that miR‐203 is associated with a more favorable prognosis.