Objective The aim was to determine the effects of chronic intermittent hypobaric hypoxia (CIHH) on prostate-specific antigen (PSA) levels in Chilean miners who work at different altitudes. Methods A cross-sectional study was conducted between April and July 2019. Miners from five mines (N=338) at different altitudes were evaluated. We recorded sociodemographic, working and altitude information. Haemoglobin oxygen saturation (SaO(2)) and haemoglobin (Hb) were measured in situ, while PSA and testosterone were analysed at a low level. Linear mixed-effect models were used to evaluate the association between PSA level and two CIHH exposures: composite CIHH (with four descriptors) and ChileStd-CIHH (CIHH Chilean standard; based on the Chilean technical guide for occupational exposure to CIHH). All models were adjusted by age, body mass index and day of the work the samples were taken. Results Highest and lowest PSA levels were found in mines >= 3000 m above sea level (mine 3: median=0.75, IQR=-0.45; mine 4: median=0.46, IQR=-0.35). In the multilevel models, the wider altitude difference between mining operation and camp showed lower PSA levels (model D: beta PSA=-0.93 ng/mL, beta(logPSA)=-0.07, p<0001), adjusted for other CIHH descriptors, SaO(2), Hb and testosterone. The descriptors of composite CIHH explained better PSA variations than ChileStd-CIHH (model D: marginal R-2=0.090 vs model A: marginal R-2=0.016). Conclusions Occupational health regulations and high altitude medicine should consider these results as initial evidence on the inclusion of new descriptors for CIHH and the possible effect of this exposure on PSA levels in this male-dominated occupational sector.