OBJECTIVE Several research groups have investigated the influence of the human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphism on head and neck cancer (HNC) susceptibility. However, the results remain inconclusive and controversial. We therefore conducted the present meta-analysis. METHODS Relevant studies were identified through a search of PubMed databases until July 2011 and selected on the basis of established inclusion criteria for publications. RESULTS A total of 8 case-control studies on the association of hOGG1 Ser326Cys polymorphism with HNC risk were included in the present meta-analysis. Overall significant associations were observed (G allele vs. C allele: OR=1.49, 95%CI=1.08-2.05, P<0.01 for heterogeneity; GG vs.CC: OR=2.30, 95%CI=1.05-5.05, P<0.01 for heterogeneity; CG vs. CC: OR=1.40, 95%CI=1.03-1.90, P<0.01 for heterogeneity; dominant model (GG+CG vs. CC): OR=1.52, 95%CI=1.06-2.16, P<0.01 for heterogeneity; recessive model (GG vs. CG+CC): OR=2.04, 95%CI=1.05-3.96, P=0.01 for heterogeneity) after excluding the studies that were not in agreement with HWE. On performance of a subgroup meta-analysis by ethnicity, significant associations were found (G allele vs. C allele: OR=1.40, 95%CI=1.001-1.95, P<0.01 for heterogeneity; GG vs.CC: OR=2.30, 95%CI=1.05-5.05, P<0.01 for heterogeneity; recessive model (GG vs. CG+CC): OR=2.04, 95%CI=1.05-3.96, P=0.01 for heterogeneity) in Caucasian populations after excluding one study not in agreement with HWE. CONCLUSIONS Our results suggested that the G allele might be associated with an increased risk of HNC in Caucasian populations.