Long non-coding RNA (lncRNA) CASC9 is reported to be a tumor promoter in oral cancer, but its mechanism in oral squamous cell carcinoma (OSCC) has not been fully explored. Our study aimed to identify the interaction between lncRNA CASC9, microRNA-545-3p (miR-545-3p), and laminin subunit gamma 2 (LAMC2) in OSCC cells. Our study confirmed that lncRNA CASC9 and LAMC2 were upregulated in OSCC, whereas miR-545-3p expression was reduced. After performing a series of cell functional experiments, it was found that knockdown of lncRNA CASC9 or LAMC2 resulted in the inhibition of proliferation, colony formation, and migration of OSCC cells, but their negative effects could be partly impaired by the miR-545-3p inhibitor. In addition, we proved for the first time that lncRNA CASC9 can sponge miR-545-3p to upregulate LAMC2. In conclusion, our study revealed that lncRNA CASC9 promotes the malignancy of OSCC cells by sponging miR-545-3p to enhance LAMC2 expression, implying that lncRNA CASC9/miR-545-3p/LAMC2 may be an intervention approach in OSCC therapy.