Reward representation in ventral striatum is boosted by perceptual novelty, although the mechanism of this effect remains elusive. Animal studies indicate a functional loop (Lisman and Grace, 2005) that includes hippocampus, ventral striatum, and midbrain as being important in regulating salience attribution within the context of novel stimuli. According to this model, reward responses in ventral striatum or midbrain should be enhanced in the context of novelty even if reward and novelty constitute unrelated, independent events. Using fMRI, we show that trials with reward-predictive cues and subsequent outcomes elicit higher responses in the striatum if preceded by an unrelated novel picture, indicating that reward representation is enhanced in the context of novelty. Notably, this effect was observed solely when reward occurrence, and hence reward-related salience, was low. These findings support a view that contextual novelty enhances neural responses underlying reward representation in the striatum and concur with the effects of novelty processing as predicted by the model of Lisman and Grace (2005).