Hypercholesterolemia is a known risk factor for cardiovascular diseases and affects a high proportion of the population. This study aimed to assess and compare the determinants of hypercholesterolemia among Chinese adults aged 18 years and above, from 2002 to 2012. The study used a stratified multistage cluster sampling method to select participants. Sociodemographic and lifestyle information was collected during face-to-face interviews. Dietary intake was calculated by 3-day, 24-h dietary records in combination with weighted edible oil and condiments. Hypercholesterolemia was defined as total cholesterol above 6.22 mmol/L (240 mg/dL) from fasting blood samples. The study included 47,701 (mean age 43.0 years) and 39,870 (mean age 51.0 years) participants in 2002 and 2010–2012 surveys respectively. The weighted prevalence of hypercholesterolemia increased from 1.6% (2.1% urban, 1.0% rural) in 2002 to 6.0% (6.4% urban, 5.1% rural) in 2012. The intake of plant-based food decreased but the intake of pork increased over the 10 years. A high intake of protein and pork, alcohol drinking and overweight/obesity were positively associated with hypercholesterolemia. Neither education nor fruit and vegetable intake were associated with hypercholesterolemia. In conclusion, the burden of hypercholesterolemia increased substantially between 2002 and 2012 in China. Unhealthy lifestyle factors and change in traditional dietary pattern were positively associated with hypercholesterolemia. Further research on the role of diet in the development and prevention of hypercholesterolemia is needed.