The summer service, from mid-June until late September, will offer round trips for 386EUR on the airline's longest routing.
The link between Chisinau and Surgut may bring oil workers to Siberia but it is also seen as offering holiday transit routes for Russians to other European destinations.
The airline has recently achieved major growth on its London route but also flies to popular European cities including Venice and Verona.
Air Moldova has a code share agreement with Russian carrier UTair for one flight a week, but is running the new service — the longest in its 22 route timetable — alone.
It is state-owned Air Molodova's fourth Russian destination.
The airline will use an Embraer 190 jet on the route, it said in a statement.