Tsai is due to meet McCarthy and a bi-partisan group of members of Congress, likely to reaffirm the need to boost cooperation between Taiwan and the US.
The two sides have no diplomatic relations, but presidents of Taiwan have made transit stops in the US before. US media say this will be the first time for talks on US soil between a leader of Taiwan and a House speaker.
Pro-Taiwan supporters have gathered in front of Tsai's hotel alongside others waving Chinese flags in protest at her visit.
China strongly opposes arrangement for meeting
Chinese Foreign Ministry spokesperson Mao Ning on Tuesday reiterated Beijing's opposition to the meeting between Tsai and McCarthy.
Mao urged the US "not to arrange for any meeting or contact between Tsai and US political figures and officials." She said the move would violate Beijing's "One China Principle."
When then-House Speaker Nancy Pelosi visited Taiwan last August, China reacted by conducting a large military drill near Taiwan.
The White House describes transit stops as "private and unofficial," and is urging China not to "use this transit as a pretext to step up any aggressive activity around the Taiwan Strait."
Tsai agrees with Guatemalan president to boost ties
Tsai arrived in Guatemala last Friday for talks with her counterpart Alejandro Giammattei. The two leaders agreed to strengthen diplomatic ties amid increasing pressure from China as it bids to isolate Taiwan.
At a joint news conference, Tsai said she expects Taiwan and Guatemala to continue to work hand-in-hand based on a strong foundation and to mutually develop a "win-win" situation.
Giammattei said that Guatemala, as a peace-loving country, is committed to respecting Taiwan's sovereignty and territorial integrity. He described diplomatic relations between Taiwan and Guatemala as so strong no one can destroy them.
China has stepped up its efforts to isolate Taiwan in the international community since Tsai became president in 2016.
On March 26, Guatemala's neighbor Honduras switched its diplomatic recognition to China, severing ties with Taiwan.
The move reduces the number of sovereign states that recognize Taiwan to an all-time low of 13.