Cross-modal interaction (CMI) could significantly influence the perceptional or decision-making process in many circumstances. However, it remains poorly understood what integrative strategies are employed by the brain to deal with different task contexts. To explore it, we examined neural activities of the medial prefrontal cortex (mPFC) of rats performing cue-guided two-alternative forced-choice tasks. In a task requiring rats to discriminate stimuli based on auditory cue, the simultaneous presentation of an uninformative visual cue substantially strengthened mPFC neurons' capability of auditory discrimination mainly through enhancing the response to the preferred cue. Doing this also increased the number of neurons revealing a cue preference. If the task was changed slightly and a visual cue, like the auditory, denoted a specific behavioral direction, mPFC neurons frequently showed a different CMI pattern with an effect of cross-modal enhancement best evoked in information-congruent multisensory trials. In a choice free task, however, the majority of neurons failed to show a cross-modal enhancement effect and cue preference. These results indicate that CMI at the neuronal level is context-dependent in a way that differs from what has been shown in previous studies.