In the present study, two nanoparticles including lactose myristoyl carboxymethyl chitosan (LMCC) and algal polysaccharide myristoyl carboxymethyl chitosan (AMCC), were obtained for hepatic-targeted Adriamycin (ADM) drug delivery systems. ADM was successfully loaded into the LMCC or AMCC nanoparticle by dialysis. The release function and liver targeting of the nanoparticles was explored, and it was revealed that ADM release from the nanoparticles was greatest at acidic pH 5.5. ADM-conjugated nanoparticles were readily taken up by HU7 human hepatocellular carcinoma cells, relative to HT22 mouse hippocampal neuron cells in vitro. In vivo, ADM-loaded nanoparticles had significant antitumor efficacy with a 62.7% inhibition rate, followed by ADM and ADM-AMCC (51.2 and 42.5%, respectively). The tissue distribution study confirmed that ADM-LMCC had an improved liver delivery efficacy, by comparison with ADM. Furthermore, a series of safety studies, including hemolysis, acute toxicity and organ toxicity, revealed that the ADM-loaded LMCC and AMCC nanoparticles had advantages over the commercially available injectable preparation of Adriamycin hydrochloride, in terms of low toxicity levels and increased tolerated dose. These results indicated that LMCC is a promising carrier for injectable ADM nanoparticle and ADM-conjugated nanoparticles may improve the efficacy of ADM by hepatic targeting.