Background: As a crucial enzyme involved in cell aerobic metabolism of the tricarboxylic acid cycle, IDH also plays important role in cancer biology. Somatic point mutations in IDH1/2 contribute to oncogenesis by promoting the production and secretion of an oncometabolite, the D-2-hydroxybutyrate, which could alter cellular metabolism and epigenetic regulation. However, data regarding the status and prevalence of IDH1 and IDH2 mutations in pan-cancer from Chinese cancer patients is limited. Methods: Ranging from Jan 14, 2020, to Oct 25, 2021, genomic DNA extracted from 5419 blood or tissue samples involving more than 22 solid tumors types were analyzed by NGS assay to investigate the landscape of IDH1/2 mutations and hotspots. Results: IDH mutations were identified in 205 cases (3.78%), of which 145 cases (2.68%) were from the IDH1 mutations group and 63 cases (1.16%) from the IDH2 mutations group. IDH1 mutations predominantly occurred in CNS tumors, melanoma, and endometrial cancer (with mutation frequencies of 26.09%, 7.41%, 5.26%, respectively), whereas IDH2 mutations occurred commonly in endometrial cancer (5.26%) and gastric cancer (2.90%). Among the 56 mutation sites found in IDH1, Y208(19.46%), R132(16.11%), and R20(12.08%) were the three major IDH1 mutations. M397, which accounts for 33.33% of all IDH2 mutation sites, was the most significantly mutated subtypes, followed by T146(4.76%). Conclusions: Compared with IDH2, IDH1 is more frequently mutated in terms of cancer species as well as shows higher mutation frequency, and our findings implicate mutations in IDH in the pathogenesis of cancers, especially CNS tumors.