Cell fusion is a complex phenomenon that is key in maintaining tissue homeostasis, particularly in aiding tissue regeneration processes. Studies show that mesenchymal stem/stromal cells (MSCs) are capable of restoring damaged tissue by adopting the phenotype of various cell types via cell fusion. As cell fusion of MSCs with cells of different origin remains poorly researched, we have developed a protocol that allows successful electrofusion between human synovium-derived MSCs and human chondrocytes. Building on from our protocol can help researchers study the cell fusion processes in the in vitro environment and could set basis for development of fusion cell-based advanced therapy medicinal products (ATMPs). In our protocol, we provide a detailed description on how to culture both of the fusion partner cells, how to carry out the modified adherence method (MAM) to achieve a high yield of successfully fused cells, and how to determine the yield of cell fusion using either methyl violet or fluorescent cell trackers.