Objective To investigate the incidence, intensity, and influencing factors of catastrophic health expenditure (CHE) among families of patients with phenylketonuria (PKU) in China and to assess the contributions of various factors to the inequity in CHE.

Methods A cross-sectional survey was conducted among 263 PKU families from 24 provinces (autonomous regions, municipalities directly under the Central Government) in China, 2025. CHE was defined according to WHO recommended threshold of 40% of household capacity-to-pay. The incidence, mean gap (MG), and mean positive gap (MPG) of CHE were calculated. The concentration index and its decomposition were employed to evaluate equity, and logistic regression was adopted to identify influencing factors.

Results The overall incidence of CHE among PKU families was 52.09% (137/263). The incidence in rural families 69.57% (112/161) was significantly higher than that in urban families 24.51% (25/102). Major risk factors for CHE included urban-rural disparity (OR = 11.18, 95%CI: 5.367–23.295) and the presence of complications (OR = 2.35, 95%CI: 1.122–4.941). The distribution of CHE demonstrated a pro-poor pattern, with a concentration index of –0.43 (95%CI: –0.52 to –0.33). The urban-rural disparity accounted for 65.53% of the total inequality.

Conclusions Families of PKU patients in China face a high risk of CHE with substantial intensity and significant pro-poor inequality. The urban-rural disparity serves as the primary driver of this inequity.