To study the expression and clinical significance of nerve axon guidance factor(SEMA3F) and neuropilin 2(NRP2) in laryngeal carcinoma tissues. Methods A total of 82 patients with laryngeal cancer admitted to our hospital from March 2016 to March 2018 were selected as the research objects. Real-time quantitative PCR was used to detect the expression of SEMA3F and NRP2 in cancer and adjacent tissues. Taking the mean expression of SEMA3F and NRP2 mRNA in cancer tissues as the boundary, the subjects were divided into SEMA3F high and low expression groups or NRP2 high and low expression groups. The relationship between the expression of SEMA3F, NRP2 and clini-copathological characteristics were analyzed statistically. The correlation between the expression of SEMA3F and NRP2 were analyzed by Pearson linear correlation analysis. The relationship of SEMA3F, NRP2 expressions with the survival and prognosis of patients with laryngeal cancer were analyzed by Kaplan-Meier survival analysis(Log-Rank test). The risk factors affecting the survival and prognosis of patients with laryngeal cancer were analyzed by multivariate COX regression analysis. Results Compared with the adjacent tissues, the expression of SEMA3F mRNA in cancer tissues was significantly lower, while the expression of NRP2 mRNA was significantly higher(all P＜0.05). The expression of SEMA3F and NRP2 in laryngeal cancer tissue was significantly negatively correlated(r=-0.561,P＜0.001). The expression of SEMA3F and NRP2 mRNA is related to the clinical stage of tumor and lymph node metastasis(all P＜0.05). The results of survival analysis showed that the 3 year overall survival rate of patients with laryngeal carcinoma with low expression of SEMA3F mRNA and high expression of NRP2 mRNA in laryngeal carcinoma tissues was significantly poor(both P＜0.05). Multivariate Cox regression analysis showed that low expression of SEMA3F, high expression of NRP2, tumor stage Ⅲ-Ⅳ and lymph node metastasis in laryngeal cancer tissues are risk factors for poor prognosis in patients with laryngeal cancer. Conclusion The expression of SEMA3F is decreased in laryngeal cancer, while the expression of NRP2 is increased, and both are related to tumor stage and lymph node metastasis, which may be a new prognostic marker of laryngeal cancer.