Tumor necrosis factor superfamily member 13 (TNFSF13) modulates cell proliferation and apoptosis and participates in the pathogenesis of solid tumors, but its role in laryngeal cancer development is not clearly defined. In order to investigate whether TNFSF13 can be used as a biomarker for diagnosis and prognosis in laryngeal squamous cell carcinoma (LSCC) and the role of TNFSF13 in laryngeal cancer carcinogenesis, we conducted immunohistochemistry and ELISA assays to evaluate the expression level of TNFSF13 in laryngeal cancer patients and the contrast. We also conducted experiments on the functional study of TNFSF13 in vitro. We found that the expression levels of TNFSF13, ki-67, and NF-kappa B p65 in LSCC tumor tissues were higher than those in vocal polyp and para-carcinoma tissues. The Spearman rank correlation analysis showed that the expression of TNFSF13 had a positive correlation with the expression of ki-67 and NF-kappa B p65. Cox regression analysis and Kaplan-Meier plots confirmed the expression level of TNFSF13 was a prognostic factor for LSCC. Moreover, the serum TNFSF13 level was significantly higher in LSCC patients than in the controls, and the serum expression level of TNFSF13 can distinguish LSCC from healthy people, precancerosis, or laryngeal benign tumor. In addition, functional study of TNFSF13 in vitro revealed that knockdown of TNFSF13 inhibited cell proliferation by inducing G1 phase cell cycle arrest in Hep-2 cells. In conclusion, TNFSF13 may be a potential novel molecular target for diagnosis and prognosis in human LSCC, and therapies that target TNFSF13 may have clinical significance for the treatment of LSCC.