Objective To investigate the role of LncRNAs-MEG3 in the carcinogenesis and progression of nasopharyngeal carcinoma (NPC) and the possible molecular mechanism. Methods qRT-PCR was used to detect the content of MEG3 and miR-543 in NPC cells. Luciferase reporter method was used to study the relation between MEG3 and miR-543, and the changes of cell proliferation and apoptosis induced by MEG3 or KLF4 were analyzed. Western blot was used to detect the expression of KLF4, Bcl-2 and Bax proteins. Results Compared with the control group, the expression of miR-543 in NPC cell line was significantly increased (P < 0.05), while the expression of MEG3 was decreased (P < 0.05). Luciferase report and Western blot showed that MEG3 could regulate the expression of KLF4 by adsorbing miR-543 to inhibit cell proliferation, promote cell apoptosis and affect the expression levels of Bcl-2 and Bax proteins. Conclusion LncRNA-MEG3 could regulate the expression of KLF4 by adsorbing miR-543 and then plays a role in inhibiting the occurrence and development of NPC. It may be a new biomarker for NPC targeted therapy.