Curcumin, a natural product isolated from the plant Curcuma longa, has a diverse range of molecular targets that influence numerous biochemical and molecular cascades. Curcumin has been shown to inhibit nuclear factor κB (NF‐κB) activation at several steps in the NF‐κB signaling pathways and thereby controls numerous NF‐κB‐regulated genes involved in various diseases. In the present study, we investigated the effect of curcumin pretreatment on 84 tumor necrosis factor‐α (TNF‐α)‐activated genes of NF‐κB pathways in K562 cells, using a real‐time PCR array. Our results show that transcription of 29 NF‐κB‐related mRNAs was significantly downregulated (CARD4, CCL2, CD40, CSF2, F2R, ICAM1, IKBKB, IKBKE, IL1A, IL1B, IL6, IL8, IRAK2, MALT1, MAP3K1, MYD88, NFKB1, NFKB2, NFKBIA, PPM1A, RAF1, RELB, STAT1, TLR3, TNF, TNFαIP3, TNFSF10, and TICAM1), whereas 10 mRNAs were induced (AGT, CASP1, CSF3, FOS, IFNG, IL10, TICAM2, TLR2, TLR9, and TNFRSF7). Western blot analysis of CD40, NFKB1 (p50), RELB, NFKBIA (IκBα), and IL10 as well as an IL8 secretion assay confirmed our results. Taken together, we show that curcumin regulates an impressive number of NF‐κB genes within the different NF‐κB signaling pathways.