Background Socioeconomic status ( SES ) is associated with health‐related quality of life ( HRQOL ) for children with critical congenital heart disease; however, literature from newly industrialized countries is scarce. Methods and Results This cross‐sectional study included 2037 surviving patients operated on for critical congenital heart disease at a tertiary hospital in China between May 2012 and December 2015. All eligible patients were aged 2 to 12 years. HRQOL was measured by the Pediatric Quality of Life Inventory 4.0 generic and 3.0 cardiac modules. Family SES was assessed by a composite of household income in the past year and occupation and education level of each parent in the family. Mean scores of major domains in HRQOL were significantly lower in the low‐ SES group than in the medium‐ and high‐ SES groups (total generic scores: 71.2±7.9 versus 75.0±8.0 and 76.0±7.9, respectively [ P <0.001]; psychosocial functioning: 70.8±9.0 versus 74.4±8.4 and 75.3±8.4 [ P <0.001]; physical functioning: 71.6±10.4 versus 76.0±9.7 and 77.1±9.4 [ P <0.001]; heart symptoms: 71.9±11.6 versus 75.7±11.0 and 76.8±10.3 [ P <0.001]; cognitive problems: 65.4±11.1 versus 69.4±12.1 and 74.6±13.6 [ P <0.001]). After adjustment for other clinical and demographic variables in the multivariable linear regression model, family SES significantly affected all dimensions of HRQOL except for treatment barriers, treatment anxiety, physical appearance and communication. Conclusions Family SES is an important factor associated with HRQOL in patients with critical congenital heart disease. Further targeted interventions to improve HRQOL that consider the family and environmental issues confronted by those who are economically disadvantaged might help these patients have better outcomes.