hOGG1 encodes a DNA repair enzyme responsible for the excision of reactive oxygen species (ROS) in damaged DNA. Previous studies have obtained inconsistent results. To validate the association between the hOGG1Ser326Cys polymorphism and lung cancer risk, we performed an updated meta-analysis of 20 studies (8739 cases and 10385 controls) using STATA version 11.1. With this approach, we tested the overall and subgroup association between the SNP and lung cancer susceptibility stratified by ethnicity, control sources, cell histotypes, and smoking status. We demonstrated a novel, significant correlation between the hOGG1 Ser326Cys polymorphism and increased lung cancer susceptibility in Caucasians. Our findings indicate a need for larger-scale studies to verify the association of this SNP with lung cancer risk in Caucasians.