In a statement, the group says it has reason to believe the four asylum seekers may have been forcibly returned to their home country. It also calls on Kyrgyzstan to "prompty and throroughly" investigate the disappearances.
Valijon Bobojonov and Saidullo Shokirov have been missing since mid-August and are feared to be back in their home city of Andijon, in eastern Uzbekistan.
The whereabouts of Bakhtiyor Ahmedov and Ilhom Abdunabiev, who disappeared on August 23, remain unknown.
Uzbekistan has denied any involvement in the disappearances.
Kyrgyz rights activists accuse their government of allowing Uzbek secret services to operate freely in the country's south.
The UN's refugee agency, the UNHCR, has said it is considering removing the 65 Uzbek refugees and asylum seekers currently living in southern Kyrgyzstan to a safer place. According to Kyrgyz activists, there are about 500 Andijon refugees in Kyrgyzstan.