The goal of this study was to develop a systemically non-toxic and stable circulation based passive targeting system for efficient anticancer treatment. Gelatin-doxorubicin (GD) and PEGylated gelatin-doxorubicin (PGD) nanoparticles were designed and their feasibilities as an anti-cancer drug were evaluated. The sizes of GD and PGD nanoparticles were about 135 and 250 nm, respectively, and they retained their structures for 2 days in PBS. Both GD and PGD had much lower cytotoxicity in vitro and in vivo than doxorubicin (DOX) at equivalent concentrations. However, PGD significantly inhibited tumor growth compared to the control and DOX treated group, and GD moderately suppressed tumor growth compared with the control but the suppressing effect of GD did not exceed that of DOX. And GD and PGD both remarkably suppressed pulmonary metastasis. We conclude that PGD is a potential cancer therapeutic, due to its excellent anti-tumor and anti-metastatic effects and low systemic toxicity.