ObjectivesTo investigate self‐reported out‐of‐pocket health care expenses, both overall and by cost type, for a large population‐based sample of Australians, by cancer status and socio‐demographic and medical characteristics.Study designCross‐sectional study.Setting, participantsNew South Wales residents participating in the 45 and Up Study (recruited aged 45 years or older during 2005–2009) who completed the 2020 follow‐up questionnaire; survey responses linked with New South Wales Cancer Registry data.Main outcome measuresProportions of respondents who reported that out‐of‐pocket health care expenses during the preceding twelve months exceeded $1000 or $10 000; adjusted odds ratios (aORs) for associations with socio‐demographic and medical characteristics.ResultsOf the 267 357 recruited 45 and Up Study participants, 45 061 completed the 2020 survey (response rate, 53%); 42.7% (95% confidence interval [CI], 42.2–43.1%) reported that overall out‐of‐pocket health care expenses during the previous year exceeded $1000, including 55.4% (52.1–58.7%) of participants diagnosed in the preceding two years and 44.9% (43.7–46.1%) of participants diagnosed with cancer more than two years ago. After adjustment for socio‐demographic factors, out‐of‐pocket expenses greater than $1000 were more likely to be reported by participants with cancer than by those without cancer (diagnosis in past two years: aOR, 2.06 [95% CI, 1.77–2.40]; diagnosis more than two years ago: aOR, 1.22 [95% CI, 1.15–1.29]). The odds of out‐of‐pocket expenses exceeding $1000 increased with area‐based socio‐economic advantage and household income, and were higher for people with private health insurance (v people with Medicare coverage only: aOR, 1.64; 95% CI, 1.53–1.75). Out‐of‐pocket expenses exceeding $10 000 were also more likely for participants diagnosed with cancer during the past two years (v no cancer: aOR, 3.30; 95% CI, 2.56–4.26).ConclusionsPeople diagnosed with cancer during the past two years were much more likely than people without cancer to report twelve‐month out‐of‐pocket health care expenses that exceeded $1000. Out‐of‐pocket expenses for people with cancer can exacerbate financial strain at a time of vulnerability, and affect health care equity because some people cannot pay for all available treatments.