Proteomics demands high resolution multidimensional separation techniques due to its extremely high complexity. Droplet microfluidics provides a series of unique advantages in manipulating micro and nanolitre samples, such as micro-volume operation, limited diffusion and none cross-contaminating, therefore has the potential to be an ideal interface strategy for multidimensional separation. Using the microchips of different structures, functions such as "droplet generation" and "oil depletion" can be realized. Based on these functions, samples can be transferred from continuous flow to segmented flow and then back to continuous flow. In this way, different separation modes can be combined. In this study, droplet technology was utilized as a novel interface strategy in combining high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Using tryptic peptides mixture as a sample, this two dimensional HPLC-CE system provided high resolution separation with a peak capacity over 3000. This proof-of-principle study has demonstrated the usefulness of droplet interface technology in multidimensional separation.