The human striatum has been previously implicated in the processing of positive reinforcement, but less is known about its role in processing negative reinforcement. In this experiment, participants learn specific approach or avoidance responses, mediated by positive and negative reinforcers respectively to investigate how affective learning and associated neural activity are influenced by the motivational context in which learning occurs. The paradigm was divided into two discrete sessions, where participants could either earn monetary rewards (approach sessions) or avoid monetary losses (avoid sessions) based on successful learning. Specifically, a conditioned cue predicted the chance to win or avoid losing money contingent on a correct button press (pre-learning trials), which upon learning led to the delivery of rewards or termination of losses (post-learning trials). Skin conductance responses (SCRs) and subjective ratings confirmed a learning effect (greater SCRs pre vs. post-learning) irrespective of reinforcer valence. Concurrently, activity in the ventral striatum was characterized by a similar learning effect, with greater responses during pre-learning. Interestingly, such learning effect was enhanced in the presence of a negative reinforcer, as suggested by an interaction between learning phase and session, highlighting the influence negative reinforcers can have on striatal circuits involved in learning and motivated behavior.