The downregulation of cell proliferation caused by inhibition of GABABR could be rescued by repression of NF‐κB. These results indicated that the critical function of GABABR/GSK‐3β/NF‐κB signaling in colorectal cancer cell proliferation, and might provide more insight into the specific roles of GABABR to lay the foundation for further clinical application. The gene discussed is NFKB1; the disease is colorectal cancer.