Researchers attribute increased incidence of colorectal cancer to environmental pollution with endocrine disruptors, including the estrogen-like substance bisphenol A (BPA). The proliferative activity, viability, and mRNA expression levels of the PIK3CA, NFkBp65, VEGFA, ESR1, HIF1a, PTEN, TP53, CD44, and CDH1 genes were evaluated in human colon adenocarcinoma HT-29 cell culture incubated with different concentrations of BPA (5, 25, and 50 μM) for 24 and 96 h. Short-term (24 h) incubation with BPA did not lead to pronounced biological effects. During prolonged incubation (96 h), 5 μM BPA decreased VEGFA mRNA expression and increased HIF1a mRNA expression, 25 μM BPA increased the expression of PIK3CA, ESR1, and HIF1a mRNAs and decreased VEGFA and CD44, and 50 μM BPA increased the expression of ESR1 mRNA and was cytotoxic. Hence, the duration of incubation and the concentration of BPA in the culture medium affect the progression of the colon cancer and its malignancy. © 2025 Elsevier B.V., All rights reserved.