Background Ideally, neural probes should have channels with a three-dimensional (3-D) configuration to record the activities of 3-D neural circuits. Many types of 3-D neural probes have been developed; however, most of them were designed as an array of multiple shanks with electrodes located along one side of the shanks. New method We developed a novel liquid crystal polymer (LCP)-based neural probe with four-sided electrodes. This probe has electrodes on four sides of the shank, i.e. , the front, back and two sidewalls. To generate the proposed configuration of the electrodes, we used a thermal lamination process involving LCP films and laser micromachining. Results The proposed novel four-sided neural probe, was used to successfully perform in vivo multichannel neural recording in the mouse primary somatosensory cortex. Comparison with existing method The multichannel neural recording showed that the proposed four-sided neural probe can record spiking activities from a more diverse neuronal population than single-sided probes. This was confirmed by a pairwise Pearson correlation coefficient (Pearson’s r) analysis and a cross-correlation analysis. Conclusion The developed four-sided neural probe can be used to record various signals from a complex neural network.