We have studied different methods for efficient DNA transfection in neuroblastoma cell line. Here we report that the optimum transfection mode by nucleofection method yielded the maximum efficiency for SK-N-SH cells. To optimize transfection we selected different methods like electroporation, liposome mediated and PEI transfection. The DNA that was transfected was pmaxGFP plasmid (3.49kb). Our results suggest that the most efficient method for DNA transfection is very important to study gene expression and regulation by finding ways to deliver DNA into the difficult to transfect mammalian cells. The transfection efficiency by electroporation was ~60-70%, Lipofection was ~ 18-20% and PEI yielded <1%.