Objective　To explore the clinical features and genetic characteristics of mitochondrial 3-hydroxy-3methylglutaryl CoA synthase deficiency（HMGSD） . Method　The clinical data of mitochondrial HMGSD in a child was retrospectively analyzed, and related literature was reviewed. Result　A 9-month-old infant was admitted to the hospital with vomiting and convulsion for the first time and fever and cough for the second time. Laboratory tests showed hypoglycemia, acidosis, abnormal liver function and coagulation dysfunction. Urine organic acid analysis indicated dicarboxylic aciduria. Genetic testing showed that there were compound heterozygous mutations in HMGCS2 gene: c.1187+1G>C in exon 6 and c.648G>T in exon 3, which had not been reported before. Progressive clinical and biochemical improvement were observed after acidosis and hypoglycemia being corrected, anti-infectious and L-carnitine treatment. The child developed normally after a follow-up of half a year. Conclusion　Clinical manifestations of mitochondrial HMGSD in children are complex and varied. Definitive diagnosis can be achieved by gene analysis. Prompt diagnosis and early treatment are essential.