Objective：This study aims to investigate the coexisting mutation of DNA methyltransferase 3A（DNMT3A）p.R882 in patients with acute myeloid leukemia（AML）and its correlation with some clinical parameters. Methods：There were 49 target genes detected by high-throughput DNA sequencing，and the mutations of DNMT3A p.R882，exon 9 of CALR gene，exon 12 of NPM1 gene，FLT3-ITD，TAD and BZIP of CEBPA were detected by genomic DNA-PCR combined with Sanger sequencing. Results：①Forty-one patients with DNMT3A p.R882 mutations were detected in 301 patients，most common in M5 subtype；nearly all DNMT3A p.R882 mutations（97.6%，40/41）carried other gene mutations，with an average of 3.17 mutations per patient，including 9 double gene mutations，12 co-existing 3 gene mutations and 19 coexisting ≥ 4 gene mutations. ②The most common genetic mutation associated with DNMT3Ap.R882 is NPM1（n=27，65.9%），followed by FLT3-ITD（n=18，43.9%），IDH1（n=9，22.0%），TET2（n=8，19.5%）and NRAS（n=6，14.6%），and so on. ③The leukocyte level of patients with ≥ 4 gene mutations was higher than that of patients with double or three gene mutations，but there was no significant difference in leukocyte，hemoglobin or platelet level（P＞0.05）. The peripheral leukocyte level of patients with FLT3-ITD gene mutations was higher than that of wild patients（P=0.034），but there was no significant difference in age，hemoglobin and platelet level. And there was no significant difference in median age and peripheral leukocyte level between NPM1，IDH1 or TET2 mutants and wild type. ④Compared with the wild type，patients with NPM1 mutations had a higher complete remission（CR）rate，while the patients with IDH1 mutations had a lower CR rate（P=0.010，0.025）. But there was no significant difference in CR rate between the patients with FLT3-ITD on TET2 mutations and the wild type. Conclusion：More than 95% of DNMT3A p.R882-mutated AML coexisted with additional gene mutations，the number and type of coexisting mutations had a certain impact on the clinical characteristics of patients.