Santa Cruz de la Sierra (Spanish: [ˈsanta ˈkɾuz ðe la ˈsjera]; lit. "Holy Cross of the Mountain Range"), commonly known as Santa Cruz, is the largest city in Bolivia and the capital of the Santa Cruz department. Situated on the Pirai River in the eastern Tropical Lowlands of Bolivia, the city of Santa Cruz and its metropolitan area are home to over 70% of the population of the department and it is one of the fastest-growing cities in the world. The city was first founded in 1561 by Spanish explorer Ñuflo de Chavez about 200 km (124 mi) east of its current location, and was moved several times until it was finally established on the Pirai River in the late 16th century. For much of its history, Santa Cruz was mostly a small outpost town, and even after Bolivia gained its independence in 1825 there was little attention from the authorities or the population in general to settle the region. It was not until after the middle of the 20th century with profound agrarian and land reforms that the city began to grow at a very fast pace.

The city is Bolivia's most populous, produces nearly 35% of Bolivia's gross domestic product, and receives over 40% of all foreign direct investment in the country. This has helped make Santa Cruz the most important business center in Bolivia and the preferred destination of migrants from all over the country.