In a large brain-imaging study, a multinational consortium has recently identified a common genetic variation in rs7294919 being associated with hippocampal volume. Here, we explored whether this quantitative trait locus also affects hippocampal function using a previously established reliable neuroimaging paradigm. We observed a significant effect of rs7294919 variation in the right hippocampus showing that hippocampal activation increased with the number of risk alleles. Furthermore, the risk allele was associated with decreased performance in a verbal learning and memory task. By showing that this single-nucleotide polymorphism also relates to behavioral difference and underlying brain activation in memory, our findings support the idea that rs7294919 may affect the individual capacity to resist disease in terms of diminishing or boosting hippocampal resources.