To investigate associations between parent–child relationships, children’s externalizing and internalizing symptoms, and lifestyle responses to the COVID-19 epidemic, we conducted an online survey of a random, representative sample of residents with children aged 3–17 years during mid-March 2020 in Wuhan and Shanghai, China. A total of 1655 parents and children were surveyed with a response rate of 80.1% in the survey. During the epidemic, the frequency of children enquiring about the epidemic (AOR = 1.46, 95% CI: 1.04, 2.06), parents explaining the epidemic to them (AOR = 2.87, 95% CI: 1.80, 4.58), parents expressing negative emotions in front of them (AOR = 2.62; 95% CI = 2.08–3.30), and parents with more irritable attitudes (AOR = 1.93; 95% CI = 1.33–2.81) were significantly associated with children’s externalizing symptoms. For internalizing symptoms, significant associations were found with worse parent–child closeness (AOR = 2.93; 95% CI = 1.80–4.79), the frequency of parents expressing negative emotions in front of them (AOR = 2.64; 95% CI = 1.68, 4.12), and more irritable attitudes (AOR = 2.24; 95% CI = 1.42–3.55). We also found that each indicator of parent–child relationships had the significantly similar associations with children’s lifestyle behaviors. These findings suggest that improving parents’ attitudes towards their children and parent–child closeness during the epidemic, especially among parents with lower educational levels, are important to ensure the wellbeing of children.