Long noncoding RNAs (lncRNAs) have emerged as new regulatory molecules implicated in diverse biological processes， including therapeutic resistance. However， the mechanisms underlying lncRNA-mediated temozolomide (TMZ) resistance in glioblastoma (GBM) remain largely unknown. To illustrate the role of lncRNA in TMZ resistance， we induce TMZ-resistant GBM cells， perform a lncRNA microarray of the parental and TMZ-resistant cells， and find an unreported lncRNA in GBM， lnc-TALC (temozolomide-associated lncRNA in glioblastoma recurrence)， correlated with TMZ resistance via competitively binding miR-20b-3p to facilitate c-Met expression. A phosphorylated AKT/FOXO3 axis regulated lnc-TALC expression in TMZ-resistant GBM cells. Furthermore， lnc-TALC increased MGMT expression by mediating the acetylation of H3K9， H3K27 and H3K36 in MGMT promoter regions through the c-Met/Stat3/p300 axis. In clinical patients， lnc-TALC is required for TMZ resistance and GBM recurrence. Our results reveal that lnc-TALC in GBM could serve as a therapeutic target to overcome TMZ resistance， enhancing the clinical benefits of TMZ chemotherapy.