OBJECTIVE Altered microRNA (miRNA) expression has been found in many cancers, including lung, breast, prostate, bladder and colorectal cancer. Many recent studies have demonstrated that aberrant plasma miRNAs were also found in various types of cancers. However, the alteration in plasma miRNA expressions in laryngeal squamous cell carcinoma (LSCC) remains unclear. The present study aimed to investigate the alterations in plasma miRNAs in LSCC. METHODS In the present study, the expression profiles of 738 miRNAs in plasma from 20 patients and 44 healthy subjects were evaluated using high-throughput real-time quantitative polymerase chain reaction. RESULTS Our results demonstrated that expression levels of 17 miRNAs were significantly upregulated in patients with LSCCs when compared to control group (p < 0.05). Expression levels of nine miRNAs were found significantly downregulated in LSCC patients (p < 0.05). In addition, 17 miRNAs were expressed only in LSCC group, and five of these miRNAs (miR-331-3p, 603, 1303, 660-5p and 212-3p) are LSCC specific and never seen before in plasma of any human subject. CONCLUSIONS In conclusion, our study suggests that detecting these LSCC-specific miRNAs in plasma might serve as novel noninvasive biomarkers for LSCC.