Colorectal cancer is considered the second most deadly cancer in the world. Studies have indicated that diet can prevent the risk of developing colorectal cancer. Recently, there has been an increasing interest in polyphenols due to their plausible effect on cancer prevention and treatment. p-Coumaric acid ( p-CouA), a phenolic compound, is a cinnamic acid derivative found in several fruits, vegetables, and herbs. A growing body of evidence suggests that p-CouA may be an effective agent for preventing and managing colorectal cancer. In this current review, we briefly highlight the bioavailability of p-CouA. We also provide an up-to-date overview of molecular mechanisms underlying its anticancer effects, focusing on anti-inflammatory and antioxidant potentials, apoptosis induction, and cell cycle blockade. Finally, we discuss the impact of p-CouA on clonogenicity and multidrug resistance of colorectal cancer cells.