This study investigated whether microRNA-183 and microRNA-141 in nasopharyngeal carcinoma (NPC) lesions are potential risk factors for poor prognosis. A total of 317 NPC patients admitted to Zhengzhou Central Hospital Affiliated to Zhengzhou University from January 2010 to March 2015 were included. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect the expression of microRNA-183 and microRNA-141 in lesions and adjacent tissues, and the relationship between the microRNA-183 and microRNA-141 expression levels and prognosis was analyzed. The expression levels of microRNA-183 and microRNA-141 in lesions were significantly higher than those in adjacent tissues (p<0.05). Patients with distant metastasis had significantly higher expression levels of microRNA-183 and microRNA-141 than patients without distant metastasis (p<0.01). Patients with disease-free survival (DFS) <3 years showed significantly higher expression levels of microRNA-183 and microRNA-141 than those with DFS ≥3 years (p<0.01). NPC patients with high expression levels of microRNA-183 and microRNA-141 showed poor prognosis. MicroRNA-183 and microRNA-141 may play an important role in the distant metastasis of NPC, and have a great impact on prognosis.