Objective.Radiotherapy delivered at an ultra-high dose rate (UHDR) is a promising cancer treatment. In the last years, it has been shown to selectively reduce toxicity in healthy tissue by triggering the so-called FLASH effect achieved through specific temporal dose fractionation. However, the increase of the instantaneous dose rate results in the production of stronger thermoacoustic emissions for microsecond or shorter pulsed ionizing beams, which could potentially impact the treatment outcomes. Focusing on scenarios expected to create the highest acoustic intensities, the objectives of this work were to assess whether acoustic resonance can theoretically occurin vivoand how it could be mitigated in cases where it would influence the biological response.Approach.Thermoacoustic emissions were retrospectively simulated from post-treatment x-ray computed tomography scans of cats irradiated with a single high dose of electron FLASH to treat squamous carcinoma of the nasal planum. The peak dose, pressure intensity and location of the acoustic resonance were assessed for different beam positioning and reproduced for three animals.Main results.Irradiation of nasal planum in cats using a frontal electron beam results in pressure hot spots due to acoustic resonance that are observed in the vicinity of the rostral maxillary bone. The pressure distribution is mostly influenced by the anatomy (i.e. geometry and heterogeneous composition of the irradiated object), whereas its intensity largely depends on the irradiation setup. While further experimental investigation is needed to understand and mitigate potential associated risks, our results underline that acoustic phenomena so far neglected in conventional radiotherapy may need to be accounted for when using UHDR delivery.Significance.We show that specific irradiation scenarios can induce geometry-dependent thermoacoustic resonancesin vivowhich may be of sufficient magnitude to induce biological effects and impact the outcomes of FLASH radiotherapy.