In this work, we aimed to increase the selectivity of lithium selective electrodes containing lithium ionophore VI in the membrane matrix by using 4, 4, 4-Trifluoro-1-phenyl-1, 3-butanedione (HBTA). Potentiometric response characteristics of the prepared lithium selective electrodes were investigated. Increasing the ratio of HBTA molecule in the membrane cocktail from 0.5% to 1.5% provided a better response with respect to the lower detection limit (LDL), linear range, and selectivity. The LDL and linear range of the electrode with 1.5% HBTA were 7.6× 10-6 mol L-1 and 1.0× 10-1 ̶ 3.4× 10-5 mol L-1 respectively, with a slope 54.3 mV/decade (R2= 0.9998). The potentiometric responses of all electrodes were pH-independent in the range of pH 3-12. The response time of the electrodes was less than 10 s and the lifetime was more than eight weeks. The electrode with 1.5% HBTA showed a better selectivity against sodium (1: 575) and potassium (1: 270) and was successfully applied for the determination of lithium levels in diluted human serum samples. The obtained potentiometric data were compared with the ICP-MS results at 98% confidence level.