Oral squamous cell carcinoma (OSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC), and the effect of zymosan (ZYM), a component of the yeast cell wall, on oral cancer remains unclear. The CCK-8 proliferation assay was performed to evaluate the effect of ZYM on the proliferation of the OSCC cell lines WSU-HN4, WSU-HN6 and CAL27, and the potential mechanism was explored by quantitative real-time PCR, immunofluorescence assay and western blot. A cell adhesion assay was conducted to determine the adhesion ofCandida albicansto OSCC cells, and the expression of related genes, includingTLR2,MyD88,NLRP3,ASC,Caspase-1andIL-1 beta, and proteins, including TLR2, MyD88, NF-kappa B p65, p-NF-kappa B p65 and E-cadherin was determined. Additionally, the pro-inflammatory cytokines including IL-6, IL-8, TNF-alpha and IL-1 beta produced by OSCC cells were detected using a chemiluminescence immunoassay (CLIA). In the current study, the CCK-8 assay showed that ZYM promoted the proliferation of WSU-HN4, WSU-HN6 and CAL27 cells via the TLR2/MyD88 pathway. The cell adhesion assay showed that the number ofC. albicanscells per field significantly increased in ZYM-treated OSCC cells compared to controls. When treated with ZYM, OSCC cells secreted significantly more pro-inflammatory cytokine IL-1 beta, which could enhance inflammation in oral cancer microenvironment. In conclusion, ZYM from the fungal cell wall promotes the proliferation,C. albicansadhesion and IL-1 beta production in OSCC, as demonstrated by in vitro experiments.