Flavones and flavonols belong to flavonoids that have anti-cancer activities. In order to explore molecular mechanism and inhibitory effects of flavones and flavonols on human esophageal carcinoma cells, the inhibition of proliferation and the induction of G2/M cell cycle arrest in KYSE-510 cells and OE33 cells treated with three flavones (luteolin, apigenin, chrysin) and three flavonols (quercetin, kaempferol, myricetin) were analyzed by MTT array and flow cytometry. Among these compounds, luteolin and quercetin were the most active flavonoid to inhibit the proliferation of KYSE-510 cells and OE33 cells, respectively. The genes related to cell cycle control were analyzed by gene chip, after KYSE-510 cells and OE33 cells were treated by luteolin and quercetin, respectively. The results were shown that the expression of p21^waf1 was induced and the expression of cyclin B1 was suppressed in KYSE-510 cells, and that the expression of GADD45β and 14-3-3σ were induced and the expression of cyclin B1 was suppressed in OE33 cells. These results were verified by real-time RT-PCR and Western-blot. The comparative effects of all six compounds on the regulation of these gene expressions at the mRNA and protein levels were also analyzed by real-time RT-PCR and Western-blot. The results were shown that p21^waf1, GADD45β, 14-3-3σ and cyclin B1 were the target genes which mediated the effects of flavones and flavonols on induction of cell cycle arrest in KYSE-510 cells and OE33 cells.