Objective：To investigate the correlation between -415T/C and -462G/A single nucleotide polymorphism in the promoter region of chromogranin A（CHGA） and prognosis of critically ill patients. Methods：Totally 294 critically ill patients consecutively ad－mitted to our ICU were recruited. The -415T/C and -462G/A genetic polymorphisms of CHGA were determined the by polymerase chain reaction and DNA sequencing technology，and correlation between genotype and clinical characteristics of patients were ana－lyzed. Results：①There was no significant difference in the minor allele frequency（MAF） of CHGA-415T/C and CHGA-462G/A ge－netic polymorphism between participants of this study and the healthy people in Asia.②The CHGA-415T/C MAF of death group was significantly higher than that of survival group（MAF 0.378 and 0.292 respectively，P=0.046），but there was no significant difference in the CHGA-462G/A genetic polymorphisms between the two groups（MAF 0.096 and 0.107 respectively，P=0.717）. ③ Survival analysis showed that there were significant differences between CHGA-415T/C mutation group（including TC and CC genotypes） and wild group（TT genotype）（Log rank=7.331；P=0.007）. The mortality in mutant group was significantly higher than that in wild group（0.325 and 0.191，respectively；P=0.010）. Binary logistic analysis showed that CHGA-415T/C polymorphism was an independent risk factor for the mortality of critically ill patients（OR=2.055，95%CI=1.051-4.019，P=0.035）. Conclusion：Critically ill patients with CHGA -415T/C mutant genotype display higher 30 d mortality than wild genotype group. Furthermore the death group had higher MAF than survival group. The CHGA -415T/C polymorphism could be an independent risk factor for 30 d mortality in critically ill patients.