Niosomes are novel means of delivering drug in controlled manner to enhance bioavailability and get therapeutic effect over a longer period of time 3-4. They are attracted great attention in delivery of drug because of their amphiphilic nature, biodegradability, non-toxicity and potential for increasing drug bioavailability 5. These are lamellar structures 10-1000 (nm) made up of amphiphilic molecules surrounded by an aqueous compartment 6,7. A number of nonionic amphiphilic surfactant materials, such as alkyl ethers, alkyl esters, polysorbates and alkyl amides and cholesterol used for formulation of niosomes and in most studies single surfactant systems are utilized 8. However, using more than one amphiphiles can improve wettability as compared to single surfactants as well as drug release and permeation profiles 9.These are useful for the delivery of both hydrophilic and hydrophobic drugs which are encapsulated in interior hydrophilic compartment and outer lipid layer respectively. PEG is a biocompatible, non-toxic and non immunogenic polymer, which is used to modulate the stability, solubility, plasmatic half life and clearance of different compounds (Immordino et al. 2006). Grafted PEG moieties onto the surface of colloidal carriers strongly reduce the carriers’ uptake by RES and prolong the blood circulation time thus improving the distribution in perfused tissues. These features are strictly related to the steric hindranceeffect of the polymer that avoid the opsonisation (Tanaka et al. 2009).As a result, liposomes modified with PEG-lipid have proved to have prolonged blood circulation time and reduced mononuclear phagocyte system uptake MPS (11).Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer representing the 85% of liver cancers Hepatocellular carcinoma (HCC) is 5th most common cancer in human which affect approx 7.5 lakhs peoples per year globally. About 7 lakhs death annually occurs by HCC which shows that the mortality of HCC is very high and has been estimated to be 3rd common cause of death by cancer effecting humans. HCC is a multistep process involving different genetic alteration ultimately leads to maleficence transformation of hepatocytes 47. In HCC oxidative stress play a major role in the progression and development of carcinogenesis. Oxidative stress activates the signaling cascade (like MAPK pathway) in hepatocellular carcinoma which can influence the regulation of cell growth and transformation process. In normal physiological condition a balance between oxidative defence and reactive oxygen species takes place in a cell. When the level of reactive oxygen species raises, it causes oxidative stress and makeup a toxic environment to the cell. This situation is responsible for the development of cancer mainly by enhancing DNA damage and by disturbing or modifying some cellular processes 3.?-Sitosterol is one of several phytosterols (plant sterols) with chemically similar to cholesterol. BS a naturally occurring sterol molecule, promotes apoptosis by increasing FAS level and caspase-8 activity(8), phosphorylation of extracellularsignal regulating kinase (ERK) and p38 mitogenactivated protein kinase (MAPK) 9, inhibition of cancer cell proliferation even at low concentrations with no cytotoxic effect to noncancerous cells 10, modulation of antioxidant enzyme levels in pathogenesis 11, arrest of cells at G2/M phase in prostate cancer cells 12, and decreasing free radical generation in vitro 13. Epidemiological evidence has shown that BS is a particularly potent inhibitor of tumor growth in human colon cancer HT-29 cells and human prostate cancer LNCaP cells 11,12. In addition, SITO has also been shown to affect growth and apoptosis in human breast cancer MDA-MB-231 cells 13,14.These epidemiological result strongly suggest that BS surface modified niosomes prevent liver cancer development.