基因组不稳定性和炎症是支持癌症发展和进展的两个关键特征。G-四链结构是导致基因组不稳定性和炎症的关键因素。过去，人们认为G-四链结构仅仅是能够阻碍致癌基因转录的障碍物。发现一种针对G-四链结构的配体具有抗癌活性，使得G-四链结构成为潜在的抗癌靶点。然而，进一步的研究揭示出G-四链结构广泛分布于人类基因组中，并具有多种功能，如调节DNA复制、DNA修复、转录、翻译、表观遗传学和炎症应答等。G-四链结构在转录和翻译中具有双重调控作用。在本综述中，我们重点关注G-四链结构作为胃肠癌治疗的新靶点。我们总结了G-四链结构在胃肠癌中的应用基础，包括它们的分布位点、结构特征和生理功能。我们描述了食管癌、胰腺癌、肝细胞癌、胃癌、结直肠癌和胃肠道间质瘤治疗的当前情况，以及相关的挑战。最后，我们回顾了G-四链结构靶点的前景临床应用，并为胃肠癌的靶向治疗策略提供参考。© 2023作者授权，由百世灯出版集团有限公司出版。保留所有权利。

Genomic instability and inflammation are considered to be two enabling characteristics that support cancer development and progression. G-quadruplex structure is a key element that contributes to genomic instability and inflammation. G-quadruplexes were once regarded as simply an obstacle that can block the transcription of oncogenes. A ligand targeting G-quadruplexes was found to have anticancer activity, making G-quadruplexes potential anticancer targets. However, further investigation has revealed that G-quadruplexes are widely distributed throughout the human genome and have many functions, such as regulating DNA replication, DNA repair, transcription, translation, epigenetics, and inflammatory response. G-quadruplexes play double regulatory roles in transcription and translation. In this review, we focus on G-quadruplexes as novel targets for the treatment of gastrointestinal cancers. We summarize the application basis of G-quadruplexes in gastrointestinal cancers, including their distribution sites, structural characteristics, and physiological functions. We describe the current status of applications for the treatment of esophageal cancer, pancreatic cancer, hepatocellular carcinoma, gastric cancer, colorectal cancer, and gastrointestinal stromal tumors, as well as the associated challenges. Finally, we review the prospective clinical applications of G-quadruplex targets, providing references for targeted treatment strategies in gastrointestinal cancers.©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.