The favorable inhibitory effect of tea polyphenols on heterocyclic aromatic amines (HAAs) has been confirmed in many past studies. The objective of this study was to investigate the structure-activity relationship of catechins that act as inhibitors of HAA formation in chemical models. Two kinds of quantitative structure-activity relationship models for catechin-inhibiting-HAA were established. We chose two kinds of HAAs including 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and five catechins including epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC), epicatechin (EC), and catechin (C). The inhibitory effect of five catechins were in the following order: EGCG > ECG > EGC > C > EC. Thereinto, EGCG and ECG showed dramatically better inhibition on the formation of PhIP and MeIQx, especially EGCG. Further, the mechanisms of catechin-inhibiting-HAA were speculated by correlation analysis. The free radical-scavenging ability was predicted to be the most relevant to the inhibitory effect of ECG, EGC, EC and C on HAAs. Differently, the phenylacetaldehyde-trapping ability might be the more important mechanism of EGCG inhibiting PhIP in chemical model system. This study may bring a broader idea for controlling the formation of HAAs according to the structure of catechins.