Aim: 1-Determine cell viability by using docetaxel and lapatinib. 2-Determine the effect of the clinically relevant drugs on the regulation genes. Methods: We employed MTT assays to evaluate the cell viability of three colorectal cancer cell lines (HT-29, HCT-116, and SW-620) following treatment with docetaxel and lapatinib. Subsequently, RNA was isolated from both treated and untreated HT-29 and HCT-116 cells. HT-29 cells were exposed to 3.9uM lapatinib and 0.027uM docetaxel, while HCT-116 cells were treated with 5.6uM lapatinib and 0.038uM docetaxel. The concentrations used were based on the IC50 values for docetaxel and lapatinib in HT-29 and HCT-116 cells. Real-time PCR analysis was conducted to confirm data. Results: The results of MTT assays demonstrated a decrease in cell viability for HT29, HCT-116, and SW-620 cells as the concentrations of docetaxel and lapatinib increased. This indicates the effectiveness of both drugs in reducing the viability of these colorectal cancer cell lines. In addition, the gene expression analysis revealed that docetaxel and lapatinib had notable effects on the genetic activity of these cells. Specifically, these drugs down-regulated genes that play crucial roles in cell proliferation, cell cycle progression, transcription factors, cell signaling, and oncogenesis. On the positive side, there was an up-regulation of genes related to inducing apoptosis, causing cell cycle arrest, and promoting cellular differentiation in all three cell lines. However, a potential concern emerged as docetaxel and lapatinib also up-regulated genes associated with chemotherapeutic resistance. This suggests a potential challenge in the form of induced resistance to these drugs by the cancer cells. Conclusions: Docetaxel and lapatinib altered numerous genes, and many of these changes may be related to the molecular processes by which these drugs inhibit the growth of colorectal cancer cells. This data may be applied to future mechanistic studies and to the development of improved therapies for colorectal cancer.