A new method for simultaneous spectrophotometric determination of Ga (III) and Tl (III) based on their complexes with 4-(2-Pyridylazo)-resorcinol (PAR) is proposed. The results of simultaneous determinations in mixture were obtained by using partial least-squares regression (PLS) and genetic algorithm-partial least squares regression (GA-PLS). Moreover, the comparison between them has been conducted. The relative error of prediction (RPE) for Ga (III) and Tl (III) were calculated to be 4.98, 8.84 from PLS and 4.83, 4.82 due to running GA-PLS respectively. The pH effect on the sensitivity and selectivity was studied according to the net analyte signal (NAS) approach. The pH was selected at 5.5 as the optimum value to compromise the sensitivity and selectivity of these metal ions. As a consequence, the GA-PLS shows better prediction ability over full spectrum of PLS.