<p>The tumor inflammatory microenvironment plays an important role in tumor development, and the compounds which modulate tumor microenvironment can be able to accelerate tumor cell death. Here, compound <b>1</b> was screened and evaluated through both inhibiting cancer cell proliferation and alleviating the inflammation in microenvironment. In the anti-cancer cell proliferation assay, compound <b>1</b> displayed strong proliferative inhibition against all six cell lines, with IC₅₀ values in the range 2–6&#xa0;μM; among them, the HCT116 cell line was the most sensitive to compound <b>1</b>. Second, compound <b>1</b> showed better inflammatory activities in RAW264.7 cell model than the control GA and 5-FU; it not only decreased the NO level in a concentration-dependent manner, but also reduced the TLR4, HMGB1, IL-1β, TNF-α, iNOS and COX-2 levels; moreover, compound <b>1</b> also strongly inhibited NO produce in A549, HEPG2, and HCT116 cells, and it displayed the best for HCT116 cells, with an IC₅₀ value of 2.04 ± 0.68&#xa0;μM. Third, compound<b> 1</b> decreased the MMP and increased ROS levels in HCT116 cells; and it upregulated the expression levels of Bax and Cyt-C, and downregulated the Bcl-2 level, finally activating caspase-3 to promote the HCT116 cells apoptosis. This indicates compound <b>1</b> had an anti-HCT116 activity possibly by inhibiting the inflammatory factors in microenvironment, as well as by inducing HCT116 cells apoptosis. In animal tests, compound <b>1</b> reduced the volume and weight of tumor, indicating it has an obvious anti-tumor effect. Overall, compound <b>1</b> is a multi-target drug for the treatment of colon cancer, and it has the potential to be an anti-colon cancer drug candidate.</p> Graphical abstract <p></p>