Objectives: To investigate the current clinical situations of uncertainty in illness of parents with congenital heart disease (CHD) children in rural areas, and to discuss the correlation of health information literacy (HIL) with mental elasticity and uncertainty in illness. Methods: Health Information Literacy Questionnaire and Parents’ Perception Uncertainty in Illness Scale (PPUS-FM) were adopted to investigate into 125 parents of CHD children in rural areas. Statistical analysis of the data obtained was conducted with SPSS22.0 software. Results: The score of uncertainty in illness of the parents of CHD children in rural areas was 102.44±21.91; the scores of 87.2% of the patients were in the medium and above level. Differences in distribution of scores of uncertainty in illness due to different average household monthly income, educational level, children’s ages, children as only child or not were of statistical significance (P<0.05). The score of HIL was 88.24±7.69, which was in the middle level. The score of mental elasticity was 69.56±6.93; the total score and scores of various dimensions were evidently lower than the national norms (P<0.05). As indicated by the results of Pearson correlation analysis, scores of all dimensions except for information morality dimension of HIL and mental elasticity were negatively correlated with the total score and scores of all dimensions of uncertainty in illness (r=−0.257~−0.179, P<0.05). Conclusion: Uncertainty in illness of the parents of CHD children in rural areas is high. HIL and mental elasticity are evidently correlated with uncertainty in illness; when HIL and mental elasticity are better, the uncertainty in illness is lower. Clinical medical care personnel should cultivate HIL and mobilize internal positive psychological resources to reduce uncertainty in illness.