Objective To explore the mechanism of LINC00662 in regulation of temozolomide resistance of glioma cells through miR-144/ COX-2 signaling. Methods qRT-PCR were used to measure the mRNA expression levels of LINC00662, miR-144, and COX-2 in glioma tissues, normal tissue adjacent to cancer, U251 cells, and U251/temozolomide ( TMZ) cells. The dual-luciferase reporter system were used to assess the regulatory relationship of LINC00662, miR-144, and COX-2. The five groups were a blank control, knockdown LINC00662 negative control(si-NC), knockdown LINC00662, and simultaneous knockdown of LINC00662 and inhibition of miR-144 expression. Cell proliferation were analyzed by CCK-8 and Edu assays. Apoptosis was evaluated by flow cytometry. Expression levels of target proteins were analyzed by Western blot. Results Compared with adjacent normal tissue, the mRNA expression levels of LINC00662 and COX-2 were significantly upregulated and the expression level of miR-144 was downregulated in glioma tissues(P< 0. 05). Compared with U251 cells, the mRNA expression levels of LINC00662 and COX-2 were significantly upregulated and the expression level of miR-144 was downregulated in U251/ TMZ cells. Dual-luciferase reporter assays showed that LINC00662 targeted miR-144, and miR-144 targeted COX-2. Compared with the si-NC group, cell proliferation of the knockdown LINC00662 group was significantly decreased, the apoptosis rate of the knockdown LINC00662 group was increased(P<0. 05), COX-2, PCNA, MRP1 and Bcl-2 protein expression levels in the knockdown LINC00662 group were significantly downregulated, and the Bax protein expression level in the knockdown LINC00662 group was upregulated(P<0. 05). Inhibiting miR-144 expression reversed the effects of LINC00662 knockdown on U251/TMZ cell proliferation and apoptosis(P<0. 05). Conclusions LINC00662 regulates the proliferation and apoptosis of glioma cells through miR-144/ COX-2 signaling and is closely related to temozolomide resistance of glioblastoma cells.