This study aims to identify the relationships that patients’ poor oral hygiene, flagellin, IL-1β, IL-6, and toll-like receptor 5 (TLR5) have with the progression of floor-of-the-mouth squamous cell carcinoma (FOM SCC). We collected venous blood samples, unstimulated saliva samples, and biopsies from the epithelial layer of the floor-of-the-mouth mucosa. Venous blood and unstimulated saliva samples were analysed using the ELISA kit protocol, and concentrations of flagellin, IL-1β, and IL-6 were calculated. In an immunofluorescence study, the biopsies were used to calculate TLR5. The average flagellin concentration value in saliva in the FOM SCC group and in the control, group was not significantly different. The average IL-1β, IL-6 concentrations in the saliva of the FOM SCC group were significantly higher than those of the control group. In the control group, the amount of TLR5 at a distance of 80 µm was lower compared with the experimental group on the healthy side and on the lesion side. After detecting changes in flagellin, IL-1β, IL-6, and TLR5, we determined that bacteria in the mouth containing flagellin may be involved in the pathogenesis of floor-of-mouth cancer.