BACKGROUND: The pathogenesis of hepatic diseases involves several cells, which complicates the delivery of pharmaceutical agents. Many severe liver diseases affecting the worldwide population cannot be effectively treated. Major hindrances or challenges are natural physiological barriers and non-specific targeting of drugs administered, leading to inefficient treatment. Hence, there is an earnest need to look for novel therapeutic strategies to overcome these hindrances. A kind of literature has reported that drug safety and efficacy are incredibly raised when a drug is incorporated inside or attached to a polymeric material of either hydrophilic or lipophilic nature. This has driven the dynamic investigation for developing novel biodegradable materials, drug delivery carriers, target-specific drug delivery systems, and many other novel approaches. OBJECTIVE: Present review is devoted to summarizing receptor-based liver cell targeting using different modified novel synthetic drug delivery carriers. It also highlights recent progress in drug targeting to diseased liver mediated by various receptors, including asialoglycoprotein, mannose and galactose receptor, Fc receptor, low-density lipoprotein, glycyrrhetinic, and bile acid receptor. The essential consideration is given to treating liver cancer targeting using nanoparticulate systems, proteins, viral and non-viral vectors, homing peptides and gene delivery. CONCLUSION: Receptors based targeting approach is one such approach that was explored by researchers to develop novel formulations which can ensure site-specific drug delivery. Several receptors are on the surfaces of liver cells, which are highly overexpressed in various disease conditions. They all are helpful for the treatment of liver cancer.