Serum interleukin-6 (sIL6) is an acknowledged predictor of all-cause mortality in older age. A common G/C polymorphism has been identified at position -174 of the IL6 gene promoter (IL6-174G>C), but its associations with sIL6 and mortality are still unclear. Data from a population-based elderly cohort (n=824) were used to study the associations of baseline sIL6 with the IL6-174 C-allele (C+) carrier status and all-cause mortality at 4 years, in the presence and absence of preexisting major diseases (PMD). Analyses were adjusted for socio-demographic factors and body-mass-index. Three-hundred-eighty-eight participants (47.1%) had PMD. Compared to the bottom sIL6 quartile, mortality increased both in presence [Hazard Ratio (HR)=3.04; 95% confidence interval (CI): 1.48-6.25] and absence of PMD [HR=3.91; 95%CI: 1.42-10.72] for the third higher sIL6 quartile, but only in presence of PMD for the top sIL6 quartile [HR=2.30; 95%CI: 1.09-4.83]. In absence of PMD, C+ carrier status did not affect both sIL6 and mortality. In presence of PMD, C+ carrier status was associated with increased baseline sIL6 [odds ratio 2.01; 95%CI: 1.25-3.22, for all sIL6 quartiles above the bottom] but not with increased mortality risk. A survival advantage was even found for C+ carriers with PMD and sIL6 in the top quartile [HR=0.31, 95%CI: 0.13-0.76]. In conclusion, although associated with increased sIL6 levels in presence of major diseases, the IL6-174 C-allele does not seem to have direct detrimental effects on survival in older age.