It is of interest to study the cytotoxicity of silibinin assisted silver nanoparticles in human colorectal (HT-29) cancer cells. Silver nanoparticles were synthesized using silibinin as a reducing agent. The synthesized silibinin assisted silver nanoparticles (SSNPs) were characterized and analyzed using a transmission electron microscope and spectrophotometer. The SSNPs synthesized in this study are spherical and their size ranges from 10 to 80 nm. HT-29 cells were treated with different concentrations (2, 4, 6, 8 and 10 ng/mL) of SSNPs and cytotoxicity was evaluated. The apoptosis was using flow cytometry. p53 protein expression using western blot. SSNPs are induced a decrease in viability and increased concentration-dependent cytotoxicity in HT-29 cells. SSNPs treatment also caused apoptosis-related morphological changes. SSNPs treatments at 8 and 16 ng/ml showed a prominent apoptotic change i.e., 70.3% and 83.6% respectively, and decreased viability of HT-29 cells 20% and 11.2% respectively as compared to control cells. SSNPs treatments induced p53 expression in HT-29 cells. Data shows that SSNPs have the potential to induce apoptosis in colorectal cancer cells. This provides insights for the further evaluation of SSNPs in fighting colon cancer.