Background: Oral squamous cell carcinoma (OSCC) is the most common subtype of head and neck squamous cell carcinoma (HNSC) and poses a serious threat to human health. The molecular mechanisms underlying the initiation and progression of OSCC are highly complex. Although notable advances have been made in diagnostic and therapeutic technologies in recent years, the five-year survival rate of patients has not improved substantially. Therefore, in-depth investigation of the molecular mechanisms of OSCC, identification of potential diagnostic and therapeutic biomarkers, and development of effective treatment strategies have become critical directions in current research. Aim: To investigate the relationship between the prognosis of HNSC/OSCC and the m7G-related lncRNA GSEC. Materials and Methods: RNA-seq transcriptome data and clinical data for HNSC were downloaded from The Cancer Genome Atlas (TCGA). Differential expression analysis of lncRNAs was performed, and differentially expressed lncRNAs were selected. Univariate Cox regression analysis was used to screen lncRNAs associated with prognosis. The random forest algorithm was employed to rank the importance of differentially expressed lncRNAs, and the top 50 lncRNAs were selected. Twenty-nine m7G-related genes were obtained from published literature. m7G-related lncRNAs were screened based on Pearson correlation analysis. The intersection of these results was taken to identify diagnostic biomarker m7G-related lncRNAs. The UALCAN database was used to analyze the expression of target m7G-related lncRNA in HNSC/OSCC. cBioPortal was used to analyze the gene mutation profile of GSEC in HNSC. Co-expressed genes of the target lncRNA in HNSC were collected via cBioPortal, filtering for genes with FDR<0.05 and R>0.4. GO/KEGG enrichment analysis was performed using the Metascape database. Immunohistochemical expression levels of the m7G-related gene were analyzed using the Human Protein Atlas (HPA) database. The expression level of the m7G-related lncRNA in cells was detected using qRT-PCR. Result: A total of 3,618 differentially expressed lncRNAs were identified in HNSC from the TCGA database, including 2,421 upregulated and 1,197 downregulated genes. Univariate Cox regression analysis showed that 1,306 lncRNAs were significantly associated with HNSC patient prognosis (P<0.05). The random forest algorithm ranked the top 50 important lncRNAs. Pearson correlation analysis (|correlation coefficient|>0.5, P<0.001) identified 310 m7G-related lncRNAs. Taking the intersection with lncRNAs significant in the random forest and univariate Cox regression analyses revealed that the m7G-related lncRNA GSEC has significant diagnostic value in HNSC, with DCPS identified as the m7G-related gene for lncRNA GSEC. GSEC/DCPS were significantly upregulated in HNSC/OSCC (P<0.05). High expression of GSEC showed value in predicting poor outcomes in OSCC (AUC=0.937). Analysis of the mutation spectrum of the target gene GSEC indicated that GSEC undergoes genetic mutations in HNSC, including amplification and altered mRNA expression levels. Enrichment analysis of GSEC co-expressed genes in HNSC (FDR<0.05, R>0.4) revealed that GO terms were primarily enriched in the endoplasmic reticulum lumen, glycoprotein metabolic process, and collagen fibril organization. KEGG pathways were mainly enriched in Protein processing in endoplasmic reticulum, Glycosaminoglycan biosynthesis-heparan sulfate/heparin, and Lysine degradation. Immunohistochemical analysis revealed high expression of DCPS, the m7G-related protein within the GSEC, in OSCC tissues compared to normal mucosal tissues. Further qRT-PCR detection demonstrated that GSEC is upregulated in OSCC cell lines relative to NHOK cells. Among the OSCC cell lines examined, CAL-27 exhibited the most pronounced upregulation of GSEC expression compared to SCC-4 and HSC-2 cells. Conclusion Bioinformatics analysis in this study revealed significant upregulation of the m7G-related GSEC/DCPS in HNSC/OSCC. Moreover, GSEC/DCPS expression was correlated with the prognosis of HNSC/OSCC. These findings suggest that GSEC/DCPS may serve as a novel molecular target for the diagnosis and treatment of HNSC/OSCC.