We present the synthesis and characterization of organic Salphen compounds containing bromine substituents at the para/ortho‐para positions, in their symmetric and non‐symmetric versions, and describe the X‐ray structure and full characterization for the new unsymmetrical varieties. We report for the first time antiproliferative activity in metal‐free brominated Salphen compounds, by evaluations in four human cancer cell lines, cervix (HeLa), prostate (PC‐3), lung (A549) and colon (LS 180) and one non‐cancerous counterpart (ARPE‐19). We assessed in vitro cell viability against controls using the MTT assay ((3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide)) and determined the concentration required for 50 % growth inhibition (IC50), together with their selectivity vs. non‐cancerous cells. We found promising results against prostate (9.6 μM) and colon (13.5 μM) adenocarcinoma cells. We also found a tradeoff between selectivity (up to 3‐fold vs. ARPE‐19) and inhibition, depending upon the symmetry and bromine‐substitution of the molecules, showing up to 20‐fold higher selectivity vs. doxorubicin controls.