To 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. Cross-sectional study. New 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. Proportions 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. Of 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). People 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.