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We investigated the effects of gene silencing mediated by small interfering RNA (siRNA) on two colorectal cancer cell lines: HT-29 and CaCo2. The HT-29 is characterized by APC gene mutation that is absent in CaCo2 cell line. In accordance with this we found an expression of c-Myc gene in HT-29 cells approximately five times more in comparison with CaCo2 cells. The expression c-Myc mRNA was determined also following siRNA transfer to cells. After c-Myc gene silencing we observed apoptosis among HT-29 cells (17%, 3 times more than in control). There were no significant difference of apoptotic cell number in CaCo2 culture with and without c-Myc silencing. The c-Myc silencing after heat-shock treatment of cells (44ºC, 40 min) for apoptosis induction lead to increasing of apoptotic cell number in both cell lines. However, silencing by siRNA of HSPA5 gene, the member of heat-shock protein 70 family, result in more effect on apoptosis for both cell lines after heat-shock in comparison with c-Myc silencing. The combined using of both mentioned gene silencing lead to 90% of apoptotic cells for HT-29 and 60% for CaCo2 that is significantly more than after heat-shock alone. The data demonstrate different effect of the same gene silencing in dependence on cancer cell genomic characteristics and significance of genes studied for development cancer treatment, especially for colon tumor with APC gene mutation.