Rapeseed phospholipids (RP), extracted from a residue of the oil processing, were used to elaborate liposomes for the encapsulation of lactoferrin (LF). Response surface methodology was used to evaluate the effect of RP concentration (3-12 mg/mL), stigmasterol concentration (0-3 mg/mL), and sonication time (0-20 min) on the encapsulation efficiency (EE) and particle size. Commercial soy phospholipids (SP) were used to prepare liposomes under the same conditions. Results show that RP-liposomes have a higher EE and a smaller particle size than those obtained using SP. Optimal conditions for the preparation of small LF-loaded RP-liposomes (< 200 nm) with the highest EE were: 10.18 mg/mL of RP, 2.23 mg/mL of stigmasterol, and 4.05 min of sonication time. EE, particle size, polydispersity index, and zeta-potential of LF-loaded RP-liposomes were: 91.94 +/- 0.61%, 148.57 +/- 2.76 nm, 0.23 +/- 0.01, and - 31.03 +/- 1.83 mV, respectively. Morphology confirmed the size, spherical shape and smooth surface of the LF-loaded RP-liposomes. These results suggest that RP-liposomes offer a novel option for stabilizing LF.