The aim of this study was to reveal the molecular characteristics of AIM 2 and TM4SF19 oligomeric protein complexes in oral squamous cell carcinoma (OSCC) and to evaluate their potential as potential biomarkers. The expression levels of AIM 2 and TM4SF19 in tumor and normal oral mucosa tissues were determined by immunohistochemistry, and their mRNA and protein levels were quantified by quantitative real-time PCR (qRT-PCR) and Western blot. Cell models for overexpression and knockdown of AIM 2 and TM4SF19 were constructed to investigate their effects on the proliferation, migration and invasion of OSCC cells. Finally, the function of AIM 2 and TM4SF19 in OSCC cells was further investigated by the apoptosis assay and cell cycle analysis. It was found that compared with normal oral mucosa, the expression of AIM2 in OSCC was significantly down-regulated, while the expression of TM4SF19 showed the opposite trend, that is, it was up-regulated in tumor tissues. qRT-PCR and Western blot results further confirmed this finding and showed that AIM2 and TM4SF19 expression levels were closely correlated with clinical stage and lymph node metastasis in OSCC patients. The overexpression of TM4SF19 promoted the malignant behavior of tumor cells. In contrast, the knock down of AIM2 and the knock down of TM4SF19 produced the opposite effect. Therefore, AIM2 and TM4SF19 are expected to be potential biomarkers for OSCC, providing new ideas for the early diagnosis and treatment of OSCC.