Inflammation has been known to affect endothelial function and is involved in the progression of erectile dysfunction (ED). Thus, our present study was conducted to investigate the association between inflammatory marker high-sensitivity C-reactive protein (hs-CRP) and ED in a Chinese male population. A total of 1515 participants with anthropometric measurements, serum analyses and hs-CRP values available were included in our cross-sectional study. Data involving socioeconomic and lifestyle factors were also collected. ED was assessed by the 5-item International Index Erectile Function (IIEF-5), and hs-CRP levels were measured by the immunoturbidimetric assay. Logistic regression was applied to estimate the association between the serum hs-CRP and the risk of ED, and receiver operating characteristics (ROC) curve analysis was performed to identify the predictive value of hs-CRP. Serum hs-CRP levels were significantly higher in ED patients, and increased progressively with the incremental severity of ED (P < 0.001 for trend). In the multivariate-adjusted model, men in the highest quartile of hs-CRP level versus those in the lowest quartile had a 50% increased likelihood for ED (OR = 1.50; 95% CI = 1.08-2.08). When subjects were stratified by age, the risk of ED was more prominently in the middle-aged and elderly men. Based on the ROC analysis, serum hs-CRP has a poor diagnostic value for ED with an AUC of 0.58 (95% CI: 0.56-0.61) but has a good diagnostic performance for differentiating severe ED (AUC: 0.79; 95% CI: 0.77-0.81). Our study indicates that increased serum hs-CRP levels are associated with the severity of ED and an increased ED risk in a Chinese male population. These findings suggest that hs-CRP may be of value as an inflammatory marker for the assessment of ED risk and may play an important role in the etiology of ED.