Several periodontitis-associated species induce genes related to cell proliferation, cell-cycle progression, apoptosis, intracellular transport, immune and inflammatory responses, carcinogenesis, and cancer progression. Here, we reviewed studies showing strong associations between gingival squamous cell carcinoma (GSCC) and three periodontitis-related oral bacteria (Porphyromonas gingivalis, Fusobacterium nucleatum, and Prevotella intermedia) in the microenvironment. These bacteria produce cytoplasmic lipopolysaccharide (LPS) and secrete cytokines and molecules related to carcinogenesis and tumor progression and metastasis. In GSCC, LPS levels are substantially elevated and assessable by functional analysis. Polymicrobial infections can synergistically induce inflammation and significantly upregulate proinflammatory molecules (e.g., interleukin [IL]-1β, IL-8, and tumor necrosis factor-α) that promote carcinogenesis. This review can facilitate the identification of novel targets for treating and preventing GSCC which is potentially associated with periodontal pathogen.