Objectives Oral squamous cell carcinoma (OSCC) is a common head and neck cancer with high incidence. Numerous reports have elucidated that long non-coding RNAs (lncRNAs) serve as crucial regulatory factors in various diseases including cancer. Nonetheless, the role of lncRNA JPX in OSCC is still not elaborated. Subjects and Methods In our research, we detected the expression of lncRNA JPX through qRT-PCR. Colony formation, EdU staining, Transwell, TUNEL, and caspase-3 activity assays were applied for estimating the function of lncRNA JPX in OSCC. RIP, pull-down, and luciferase reporter experiments were adopted to examine the interrelations between lncRNA JPX, miR-944, and CDH2. Results LncRNA JPX was discovered as highly expressed in OSCC cells. Silencing lncRNA JPX restrained OSCC cell proliferation, migration, and invasion. Interestingly, lncRNA JPX bound with miR-944 and then augmented CDH2 via a competing endogenous RNA (ceRNA) mechanism. Importantly, overexpressed CDH2 recovered the suppression of silenced lncRNA JPX on the oncogenic behaviors of OSCC cells. Conclusions In short, lncRNA JPX contributes to OSCC cell proliferation, migration, and invasion via miR-944/CDH2 axis, which offers a new direction for potential targeted treatment of OSCC.