There were limited studies that have probed into the combined effect of the cortisol/testosterone (C/T) ratio as a biomarker of stress and Pittsburgh Sleep Quality Index (PSQI) on coronary heart disease (CHD). This research aimed to explore the association of C/T ratio and PSQI with the risk of CHD in a rural Chinese population, as well as the interaction and combined effect between C/T ratio and PSQI on CHD. A case-control study was performed including 307 individuals without CHD and 307 patients drawn from Henan Rural Cohort. Logistic regression was utilized to survey the independent and joint effects of the C/T ratio and PSQI on CHD. To estimate the interaction impact of the C/T ratio and sleep quality (PSQI) on CHD, a cross-product term was introduced in the generalized linear model. Higher C/T ratio and PSQI index scores are related to increased odds ratio for CHD (Odds ratios (ORs) and 95% confidence interval (CI) were 1.17 (1.07, 1.29), p-trend<0.001; 1.16 (1.09, 1.22), respectively). The odds ratio of C/T ratio for CHD increased with increasing PSQI in women (pinteraction=0.018) and total population (pinteraction=0.033). The combined group of high C/T ratio and high PSQI had the highest risk of CHD (Total: OR=7.53, 95% CI: 4.12-13.76). The risk of CHD was associated with low testosterone levels, high C/T ratios, and high PSQI scores. Additionally, poor sleep quality aggravated the effect of high C/T ratio on coronary heart disease.