Emotion-cognition interactions are critical in goal-directed behavior and may be disrupted in psychopathology. Growing evidence also suggests that emotion-cognition interactions are modulated by genetic variation, including genetic variation in the serotonin system. The goal of the current study was to examine the impact of threat-related distracters and serotonin transporter promoter polymorphism (5-HTTLPR/rs25531) on cognitive task performance in healthy females. Using a novel threat-distracter version of the Multi-Source Interference Task specifically designed to probe emotion-cognition interactions, we demonstrate a robust and temporally dynamic modulation of cognitive interference effects by threat-related distracters relative to other distracter types and relative to no-distracter condition. We further show that threat-related distracters have dissociable and opposite effects on cognitive task performance in easy and difficult task conditions, operationalized as the level of response interference that has to be surmounted to produce a correct response. Finally, we present evidence that the 5-HTTLPR/rs25531 genotype in females modulates susceptibility to cognitive interference in a global fashion, across all distracter conditions, and irrespective of the emotional salience of distracters, rather than specifically in the presence of threat-related distracters. Taken together, these results add to our understanding of the processes through which threat-related distracters affect cognitive processing, and have implications for our understanding of disorders in which threat signals have a detrimental effect on cognition, including depression and anxiety disorders.