The purification of air polluted by volatile organic compounds (VOCs) using the TiO2-mediated photocatalytic oxidation (PCO) method was analyzed from a hygienic point of view by the evaluation of the total hazard during the process. For this purpose, the photocatalytic oxidation of various VOCs, including acetone, alcohols, hydrocarbons, and heteroatomic compounds, was investigated in a static reactor using an FTIR in situ method for the identification and quantitative analysis of the reaction components in the gas phase. The change in hazards during the PCO process was calculated using two hazard indexes, the maximum hazard quotient (MHQ) and the total hazard index (THI), which include the contribution of all the reaction components and be the quantitative characteristics for the estimation of the PCO purification efficiency from a hygienic point of view. The results for all the VOCs considered showed the fundamental ability of the PCO method to decrease the hazards in polluted air. The hazard indexes depended on the UV irradiation time and the type of VOC. For VOCs that are photocatalytically oxidized without the formation of gaseous intermediates, the hazard indexes initially decreased as the concentration of the VOC decreased but then slightly increased at the end of the PCO process mainly due to the accumulation of CO, which was formed as a final by-product. The TiO2 modification with Pt was shown to completely or partially suppress CO accumulation during the PCO process and to increase the efficiency of air purification from a hazard index point of view. For the photocatalytic oxidation of VOCs that results in the formation of gaseous intermediates, the hazard may increase during the PCO process and even be much higher than the initial level because such intermediates (i.e., aldehydes, acids, and inorganic compounds) have extremely low threshold limit values. Under long-term UV irradiation, all the intermediates were completely oxidized, and the hazard levels substantially decreased compared to the initial level.