TFA is used as a strong acid to remove protecting groups such as Boc used in organic chemistry and peptide synthesis.

[8][9] At a low concentration, TFA is used as an ion pairing agent in liquid chromatography (HPLC) of organic compounds, particularly peptides and small proteins.

[12] TFA is harmful when inhaled, causes severe skin burns and is toxic for aquatic organisms even at low concentrations.

Inhalation symptoms include mucus irritation, coughing, shortness of breath and possible formation of oedemas in the respiratory tract.

[13] Although trifluoroacetic acid is not produced biologically or abiotically,[14] it is a metabolic breakdown product of the volatile anesthetic agent halothane.

[21] Trifluoroacetic acid degrades very slowly in the environment and has been found in increasing amounts as a contaminant in water, soil, food, and the human body.

[27] In October 2024, a publication proposed classifying TFA as a planetary boundary threat, similar to how CFCs are treated.