Previously, we have synthesized a series of 2-styrylchromones that exhibited anticancer effect against carcinoma cells (EJMC, 2009, 44(6), 2552-2562). In this study, we initially focused on the structural modific- ations on B-ring while A-ring was free of substitution. The synthetic route of 2-styrylchromones was carried out in three steps that afforded 52a-q based on the abovementioned work. With seventeen analogs in hand, we examined their growth inhibition on a panel of carcinoma cell lines. Interestingly, 52d, 52l and 52q bearing 4’-methoxy, 3’,4’-difluoro and 3’,4’,5’-trimethoxy groups showed superior antiproliferative effect against all cell lines with GI50 values between 2 to 23μM. Due to the higher sensitivity of AGS in response to 52q-mediated growth inhibition, the 3’,4’,5’-trimethoxy groups on B-ring of 52q were remained while A-ring was modified with methoxy groups at different positions that obtained with 52r-v. All analogs exhibited antiproliferative effect against AGS cell line with GI50 values of 1.3 to 24 μM. Further demethylation of 52q to 52v mediated by boron tribromide (BBr3) afforded polyhydro- xyl derivatives 55a–e. To our surprise, none of them exhibited growth inhibitory effect against all cell lines. In summary, we demonstrated that the antiproliferative effect induced by 2-styrylchromes may be attribute- able to stereoelectronic effects as well as hydrophobicity for appropriate activity.