ObjectivesThe overdose epidemic was designated a 'Public Health Emergency' in the USA on 26 October 2017, bringing attention to the severity of this public health problem. The Appalachian region remains substantially impacted by the effects from years of overprescription of opioids, and subsequently opioid non-medical use and addiction. This study aims to examine the utility of the PRECEDE-PROCEED model constructs (ie, predisposing, reinforcing and enabling factors) to explain opioid addiction helping behaviour (ie, helping someone who has an opioid addiction) among members of the public living in tri-state Appalachian counties.DesignCross-sectional study.SettingRural county in the Appalachian region of the USA.ParticipantsA total of 213 participants from a retail mall in a rural Appalachian Kentucky county completed the survey. Most participants were between the ages of 18 and 30 years (n=68; 31.9%) and identified as men (n=139; 65.3%).Primary outcome measureOpioid addiction helping behaviour.ResultsThe regression model was significant (F-(6,F- 180)=26.191, p<0.001) and explained 44.8% of the variance in opioid addiction helping behaviour (R-2=0.448). Attitude towards helping someone with opioid addiction (B=0.335; p<0.001), behavioural skills (B=0.208; p=0.003), reinforcing factors (B=0.190; p=0.015) and enabling factors (B=0.195; p=0.009) were all significantly associated with opioid addiction helping behaviour.ConclusionsPRECEDE-PROCEED model constructs have utility to explain opioid addiction helping behaviour among individuals in a region greatly impacted by the overdose epidemic. This study provides an empirically tested framework for future programmes addressing helping behaviour related to opioid non-medical use.