OBJECTIVES: To compare cancer information (CI) seekers’: a) most recent CI-seeking experiences, and b) self-efficacy (SE) in seeking CI across demographics, healthcare access, and health status. METHODS: Cross-sectional, retrospective study was conducted on a representative, non-institutionalized sample of the U.S. population using HINTS-4 Cycle-2 data. Study sample consisted of individuals who looked for CI from any source (N=1097). Response categories for all CI-seeking experience except for ‘concern about quality of information’ were dichotomized as ‘yes’ and ‘no’. Similarly, response categories for self-efficacy in seeking CI were combined to form ‘low SE’, ‘moderate SE’, and ‘high SE’. Chi-square goodness-of-fit test was applied to all variables with significance level of 0.05. Cross tabulations, Chi-square analyses were conducted, and weighted percentages were computed using SAS® version 9.3. Results with p≤0.05 were considered statistically significant. RESULTS: Greater proportion of CI seekers had characteristics as being female, Non-Hispanic White, some college degree, higher annual income, married, employed, having insurance, having a regular provider, without personal cancer history, with family history of cancer, or with ‘excellent’ or ‘very good’ current health. Effort required to seek CI differed significantly across age, race/ethnicity, education, annual income, marital status, occupation, and personal cancer history. Feeling frustrated while seeking CI differed significantly across age, annual income, marital status, and personal cancer history. CI seekers’ concern about quality of information differed significantly across annual income, insurance, and personal cancer history. Difficulty in understanding information differed significantly across insurance. Individuals’ self-efficacy in seeking CI did not differ significantly across any study variables. CONCLUSIONS: Generally, CI-seeking experiences are likely to vary with age, race/ethnicity, education, annual income, occupation, marital status, and personal cancer history. Findings of this study may be useful in improvising current health communication interventions and to develop messages that are easily accessible and comprehendible by the American public.