Laryngeal cancer is a relatively uncommon malignancy with predisposing genetic factors that remain unclear. Single-nucleotide polymorphisms (SNPs) in genes involved in innate immune signaling may contribute to the development and progression of laryngeal carcinoma. This study aimed to evaluate the association of TLR4 (rs7037225, rs11536889, rs7037117) and MYD88 (rs7744, rs6853) polymorphisms with the risk of laryngeal squamous cell carcinoma (LSCC), as well as its clinical and pathological characteristics and survival. A retrospective case–control study involving 172 LSCC patients and 220 healthy controls was conducted. Genotyping was performed using real-time PCR from venous blood samples. MYD88 rs7744 was significantly associated with tumor size and lymph node involvement. Survival analysis showed a significant association between rs7744 and recurrence-free survival (RFS), with the AG and GG genotypes linked to poorer outcomes. Conversely, carriers of the TLR4 rs7037225 CT genotype showed significantly improved RFS, with p ranging from 0.024 to 0.037 across models. Considering the significant roles of TLR4 and MYD88 in Toll-like receptor signaling, these findings may reflect the involvement of innate immune pathways in LSCC progression. In summary, MYD88 rs7744 was associated with clinicopathological features and RFS, while TLR4 rs7037225 appeared to have a potential protective effect on survival.