Background: Colorectal cancer (CRC) is a frequently occurring malignant tumor, which is mainly observed in elderly men with no significant symptoms at the early stage. Among the malignant tumors of the digestive system, the incidence and mortality of CRC rank second only to hepatic and gastric cancer. Curcumin is an antioxidant and anti-inflammatory compound extracted from the roots of Curcuma longa plant. The antitumor effects of curcumin have been widely reported for various types of cancers, including CRC. Objective: In this study, we aimed to elucidate the protective effects and mechanism of interleukin (IL)-1 β on curcumin-induced apoptosis in SW480 cells. Materials and Methods: Expression levels of IL-1 β in CRC tissues and cells were detected by the quantitative reverse transcription polymerase chain reaction and Western blot assays. Followed by the incubation of cells with curcumin, the effect on IL-1 β was measured. Moreover, after transfection, the effects of IL-1 β on curcumin-induced SW480 cellular processes were analyzed by cell counting kit-8 and flow cytometric analysis. Results: According to the results of this study, IL-1 β was significantly increased in CRC tissues and cells. However, after incubation of the cells with curcumin, IL-1 β was downregulated and overexpression of IL-1 β counteracted the antitumor functions of curcumin in SW480 cells. Further studies have shown that curcumin could promote apoptosis of SW480 cells by inhibiting nuclear factor-κB (NF-κB) signaling pathway. Conclusion: Our study validated that curcumin inhibits SW480 cell proliferation but promotes apoptosis by downregulating the expression of IL-1 β probably through NF-κB signaling pathway. IL-1 β may an important target for the treatment of CRC.