Abstract: Objective: To establish a high performance liquid chromatography-electrochemical detection (HPLC-ECD) method for the determination of polyphenolic compounds in the leaves of Houttuynia cordata and investigate the contribution of different compounds to the antioxidant activity by the correlation analysis. Methods: The leaves of Houttuynia cordata were extracted by ultrasonic extraction with 80% (v/v) methanol, and the content of 12 polyphenolic compounds was determined by the established HPLC-ECD method. The total phenolics content of Houttuynia cordata leaves was determined by the Folin-ciocalteu method. The antioxidant activities were evaluated by radical scavenging ability and ferric reducing antioxidant power (FRAP). Cluster heat map and gray correlation analysis were used for multivariate statistical analysis. Results: The established HPLC-ECD method showed good linearity, precision, repeatability and stability, with an average recovery of 93.25%~103.97% and RSD value of 1.99%~4.47%. The total phenolic content of Houttuynia cordata leaves from different sources ranged from 5.98~52.86 mg GAE /g, which was significantly correlated with ABTS⁺, DPPH radical scavenging ability and ferric ion reduction ability (P<0.05). The polyphenolic compounds with high content in Houttuynia cordata were derivatives of caffeic acid and quercetin. All of the 12 phenolic compounds had a high degree of correlation with antioxidant activity, among which isoquercitrin, quercetin, isochlorogenic acid A, hyperoside and rutin were the highest. The present study clarified the primary antioxidant in Houttuynia cordata leaves, which would provide reference for the quality evaluation and resource development of Houttuynia cordata.