Try this:

Global searching/indexing uses global-messages-db.sqlite as a search index. It contains a copy of all of your messages.

If you have a IMAP account and disable offline folders it will use a background process to download copies of the messages in all of your folders. Otherwise it copies them from the mbox files.

You can disable this feature using: 'Tools' > 'Options' > 'Advanced' > 'General' tab > uncheck /deselect 'Enable Global Search and Indexer'. click on OK

make hidden files and folders visible:

• http://kb.mozillazine.org/Show_hidden_files_and_folders

In Thunderbird:

• Help > Troubleshooting Information
• click on 'Show Folder' button

a new window opens showing your Profile folder name.

• Close thunderbird new - this is important.

scroll down, locate and delete the following file(s):

• global-messages-db.sqlite

if you see this file delete it as well.

• global-messages-db.journal

Restart Thunderbird and report back on result.

I tried that. Uncheck the box and choose OK. Quit tbird, start it again and the box is checked again.

This has been happening for the past few versions. I also tried a totally fresh profile and the exact same thing.

Can you confirm that you do not use CCleaner ? I'm wondering if something keeps deleting changes in the background?

It is not a good idea to run CCLeaner on any Thunderbird folder. As it can mess about with session and saved passwords etc. If you use it, check it doesn't run in the background or at least make all Thunderbird program folders and your profile folders are exempt. I just need to rule it out.

Also check that no addons are causing the issue. Restart Thunderbird in Safe mode. Help > restart with addons disabled. Then try uncheck /deselect 'Enable Global Search and Indexer'.

Don't have CCleaner. (not familiar with it).

I chose "restart with addons disabled" checked "Disable all add-ons" in the popup and "make changes and restart". Then I unchecked the global indexer and did the same restart with addons disabled.

This time the checkbox for global search remained switched off so it's one of the addons.

I re-enabled my addons one at a time checking the indexer setting each time. Soon as I enabled the "Exchange EWS Provider" the global indexer setting came back on. I double checked by re-disabling the EWS provider and it confirmed that's what's causing it.

I'll submit a bug report to the author/maintainer of that addon.