A potentiometric flow injection system was adopted by using a Li+-selective electrode with improved selectivity for sensitive and selective determination of Li+ in human serum spiked samples. For the optimization of the offered flow injection system, multivariate method was utilized. Potentiometric characteristics of the system were investigated (linear range: 5.0x1051.0x101molL1, slope: 56.93mV per decade, detection limit: 3.4x105molL1, sampling-rate: 40 injections per hour). The detection of Li+ in real serum samples was achieved. The obtained results for the spiked serum samples were in good agreement with IC results at 95% confidence level.