Phytosterols and related derivatives phytostanols are naturally occurring bioactive compounds present mainly in plant cell membranes. These lipophilic steroid alcohols contain a tetracyclic cyclopenta [a] phenanthrene structure which is substituted with a hydroxyl group at position C3 and have a side chain at position C17, usually containing one or more double bonds in the steroid skeleton. Phytosterols derived from isopentenyl pyrophosphate belong to the terpene family and are generally synthesized by the mevalonate pathway. They have similar structural and biological functions to cholesterol. It is not possible to synthesize by a human; as a result of their intake in diet, they are present in the human body as cereals, legumes, vegetables, fruits, nuts, vegetable oils, oilseeds, cereal grains, cereal-based products and related products which contain phytosterols in relatively high amount, consumed daily by the whole world population. Phytosterols are known as part of the normal human diet. Increasing interest has been given to phytosterols in recent years as epidemiological and experimental studies suggest that they have an important role in the protection from cancer besides their several beneficial effects, such as anti-inflammatory, antioxidative, anticarcinogenic, antifungal, antibacterial, antipyretic, antineoplastic, anti-ulcerative activity and cholesterol-lowering capacity. Inhibition tumor cell growth, multiplication, invasion and metastasis; reducing cell proliferation and increasing apoptosis; decreasing tumor size; inhibition of carcinogen production; reduction of angiogenesis and adhesion of cancer cells; inhibition of reactive oxygen species production and oxidative stress and increased antioxidant enzymes have been suggested as responsible mechanisms for anticancer activity of phytosterols. The current review aims to summarize the occurrence, safety, toxicity and chemistry of phytosterols to explain their potential activities in cancer with suggested mechanisms in detail. Furthermore, epidemiological and experimental studies related to treating the activity of phytosterols in gastrointestinal system cancers have been described.