The inflammatory process is related to oxidative stress and inflammation was proven to be a strong determinant of the aging process and to ultimately lead to death. The aim of the present study was to assess if, in a population of older adults, the effect of antioxidant genes GSTM1 and GSTT1 genotypes on mortality may differ depending on levels of inflammation.Data are from 353 older persons aged ≥80 years enrolled in the ilSIRENTE study. Study population was divided into two groups computed based on the median value of serum IL-6 (low IL-6, n=177 and high IL-6, n=176). All participants were followed up for 48 months.Mean age of study participants was 85.8 years (Standard Deviation 4.8), 235 (66.6%) were women. Overall 48/177 participant (27.1%) in the low IL-6 group died during the study period, compared with 97/176 (55.1%) in the high IL-6 group (p<0.001). After adjusting for potential confounders, GSTM1 wildtype had no effect on mortality in the low IL-6 group (RR=1.07; 95% CI 0.46-2.47), but it was associated with a significant lower mortality rate in the high IL-6 level (RR=0.33; 95% CI 0.15-0.69). Testing the interaction between IL-6 and GSTM1 genotype, we found a significant result (p=0.02). No significant effect of GSTT1 genotype on mortality was shown in participants with low and high IL-6 level.GSTM1 wildtype is associated with reduced mortality among older adults with high levels of inflammation, but not among those with low levels of inflammation.