Iodine-131 (¹³¹I, I-131) is an important radioisotope of iodine discovered by Glenn Seaborg and John Livingood in 1938 at the University of California, Berkeley. It has a radioactive decay half-life of about eight days. It is associated with nuclear energy, medical diagnostic and treatment procedures, and natural gas production. It also plays a major role as a radioactive isotope present in nuclear fission products, and was a significant contributor to the health hazards from open-air atomic bomb testing in the 1950s, and from the Chernobyl disaster, as well as being a large fraction of the contamination hazard in the first weeks in the Fukushima nuclear crisis. This is because ¹³¹I is a major fission product of uranium and plutonium, comprising nearly 3% of the total products of fission (by weight). See fission product yield for a comparison with other radioactive fission products. ¹³¹I is also a major fission product of uranium-233, produced from thorium.

Due to its mode of beta decay, iodine-131 causes mutation and death in cells that it penetrates, and other cells up to several millimeters away. For this reason, high doses of the isotope are sometimes less dangerous than low doses, since they tend to kill thyroid tissues that would otherwise become cancerous as a result of the radiation. For example, children treated with moderate dose of ¹³¹I for thyroid adenomas had a detectable increase in thyroid cancer, but children treated with a much higher dose did not. Likewise, most studies of very-high-dose ¹³¹I for treatment of Graves' disease have failed to find any increase in thyroid cancer, even though there is linear increase in thyroid cancer risk with ¹³¹I absorption at moderate doses. Thus, iodine-131 is increasingly less employed in small doses in medical use (especially in children), but increasingly is used only in large and maximal treatment doses, as a way of killing targeted tissues. This is known as "therapeutic use".

Iodine-131 can be "seen" by nuclear medicine imaging techniques (e.g., gamma cameras) whenever it is given for therapeutic use, since about 10% of its energy and radiation dose is via gamma radiation. However, since the other 90% of radiation (beta radiation) causes tissue damage without contributing to any ability to see or "image" the isotope, other less-damaging radioisotopes of iodine such as iodine-123 (see isotopes of iodine) are preferred in situations when only nuclear imaging is required. The isotope ¹³¹I is still occasionally used for purely diagnostic (i.e., imaging) work, due to its low expense compared to other iodine radioisotopes. Very small medical imaging doses of ¹³¹I have not shown any increase in thyroid cancer. The low-cost availability of ¹³¹I, in turn, is due to the relative ease of creating ¹³¹I by neutron bombardment of natural tellurium in a nuclear reactor, then separating ¹³¹I out by various simple methods (i.e., heating to drive off the volatile iodine). By contrast, other iodine radioisotopes are usually created by far more expensive techniques, starting with cyclotron radiation of capsules of pressurized xenon gas.

Iodine-131 is also one of the most commonly used gamma-emitting radioactive industrial tracer. Radioactive tracer isotopes are injected with hydraulic fracturing fluid to determine the injection profile and location of fractures created by hydraulic fracturing.

Much smaller incidental doses of iodine-131 than those used in medical therapeutic procedures, are supposed by some studies to be the major cause of increased thyroid cancers after accidental nuclear contamination. These studies suppose that cancers happen from residual tissue radiation damage caused by the ¹³¹I, and should appear mostly years after exposure, long after the ¹³¹I has decayed. Other studies did not find a correlation.