Paclitaxel and sorafenib loaded albumin nanoparticles (PTX-SRF-BSA-NPs) were prepared and studied here to avoid the toxicities from the excipients in the Taxol (R) and explore the effect of such combination on the antitumour efficacy and toxicity. PTX-BSA-NPs and so on were used as controls. The particle size, zeta potential, encapsulation efficiency and morphology were evaluated. Less than 70% of each drug released within 24 h. PTX and SRF existed as molecular or amorphous form in the PTX-SRF-BSA-NPs. The particle size did not change much after 2-month storage in freeze-dried form or 24 h in suspension. The treatment with PTX-SRF-BSA-NPs (7.5mgkg(-1) PTX + 7.5mgkg(-1) SRF) exhibited lower myelosuppression than PTX-BSA-NPs (15mgkg(-1) PTX) while it remained or increased the antitumour effect in mice tumour models. Compared with the solution containing the same level of PTX and SRF, PTX-SRF-BSA-NPs demonstrated significantly lower haemolysis and myelosuppression effect.