Housing hardship can create a range of health issues. However, little attention has been paid to the relationship between housing hardship and cancer incidence. This study examines the Yangtze River Economic Belt (YREB) in China as a case study to develop a model of factors related to housing hardship that can affect cancer incidence. This study employs spatial regression models to investigate the correlation between housing hardship and cancer incidence and further explores the variation in the correlation between urban areas (UAs) and non‐urban areas (NUAs). The research conclusions are as follows: (a) a palpable correlation exists between housing hardship and cancer incidence. The housing price‐to‐income ratio (HPIR) and the rental household proportion (RHP) are positively correlated to cancer incidence, whereas the per capita living area (PCLA) has a negative correlation with cancer incidence. (b) The differences in the impact of housing hardship on cancer incidence between the UAs and the NUAs are reflected mainly in the differences in the PCLA and the RHP. The PCLA has a strong association with cancer incidence in the UAs, whereas the RHP demonstrates a strong correlation with cancer incidence in the NUAs. (c) Significant spatial heterogeneity is observed in housing hardship in the YREB.