This paper investigated the extraction and separation of lanthanum(III), praseodymium(III) and neodymium(III) from aqueous hydrochloric acid solutions using a mixture of di-(2-ethylhexyl) phosphoric acid (D2EHPA) with three other extractants, namely bis(2,4,4-trimethylpentyl) phosphinic acid (Cyanex272), trioctylphosphine oxide (TOPO) and tri butyl phosphate (TBP) diluted in kerosene. In this study, the O/A = 1, T = 25 °C (room temperature), contact time of 10 minutes for the two phases, and kerosene as the diluent were chosen for all experiments. The effective factors studied in this research included the type and concentration of extractants as well as the pH of solutions. The Design Expert software was employed for the design of experiments, investigating the factors effect on the solvent extraction and the separation factor (β), and obtaining the optimal values of the factors. After a thorough analysis of the experiments, it was concluded that these factors were independent and had no interaction on each other. The maximum extraction and separation of Pr(III) and Nd(III) were attained by the mixture of D2EHPA and Cyanex272 in which the ratio of D2EHPA to Cyanex272 equaled 0.5 at pH = 4.4. Their extraction values were 90.5%, 91.3% respectively and β(Nd+Pr)/La = 14.4. In this condition, the extraction of La(III) was 50.81%. Based on this data, a two-stage extraction was used for the separation of Nd and Pr from the La, with an extraction efficiency of 97.5%, 96.9%, and 28.3% for Nd, Pr, and La, respectively. In order to selectively remove the co-extracted La from the loaded organic phase (D2EHPA + Cyanex272), the scrubbing of La was carried out with a new immiscible aqueous solution of Nd with the concentration of 251 mg/L as the scrubbing solution with a scrubbing efficiency of 85%.